Array ( [0] => {{short description|Activation or suppression of the immune system to treat disease}} [1] => {{For|the academic journal|Immunotherapy (journal)}} [2] => {{multiple issues| [3] => {{more medical citations needed|date=April 2018}} [4] => {{primary sources|date=April 2018}} [5] => }} [6] => {{Infobox medical intervention [7] => | Name = Immunotherapy [8] => | Image = CAR T-cell Therapy.svg| [9] => | Caption =The diagram above represents the process of chimeric antigen receptor T-cell therapy (CAR), this is a method of immunotherapy, which is a growing practice in the treatment of cancer. The final result should be a production of equipped T-cells that can recognize and fight the infected cancer cells in the body. {{ordered list [10] => |1=T-cells (represented by objects labeled as 't') are removed from the patient's blood. [11] => |2=Then in a lab setting the gene that encodes for the specific antigen receptors are incorporated into the T-cells. [12] => |3=Thus producing the CAR receptors (labeled as c) on the surface of the cells. [13] => |4=The newly modified T-cells are then further harvested and grown in the lab. [14] => |5=After a certain time period, the engineered T-cells are infused back into the patient. [15] => }} [16] => | ICD10 = [17] => | ICD9unlinked = [18] => | MeshID = D007167 [19] => | OPS301 = {{OPS301|8-03}} [20] => | OtherCodes = [21] => }} [22] => '''Immunotherapy''' or '''biological therapy''' is the treatment of [[disease]] by activating or suppressing the [[immune system]]. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherapies that reduce or suppress are classified as ''[[Immunosuppression|suppression immunotherapies]]''. Immunotherapy is under preliminary research for its potential to treat various forms of [[cancer]].{{Cite web|url=https://www.mskcc.org/cancer-care/diagnosis-treatment/cancer-treatments/immunotherapy|title=Immunotherapy {{!}} Memorial Sloan Kettering Cancer Center|website=mskcc.org|access-date=2017-07-27|archive-date=2019-10-19|archive-url=https://web.archive.org/web/20191019141622/https://www.mskcc.org/cancer-care/diagnosis-treatment/cancer-treatments/immunotherapy|url-status=live}}{{cite journal | vauthors = Syn NL, Teng MW, Mok TS, Soo RA | title = De-novo and acquired resistance to immune checkpoint targeting | journal = The Lancet. Oncology | volume = 18 | issue = 12 | pages = e731–e741 | date = December 2017 | pmid = 29208439 | doi = 10.1016/s1470-2045(17)30607-1 }}{{cite journal | vauthors = Conforti L | title = The ion channel network in T lymphocytes, a target for immunotherapy | journal = Clinical Immunology | volume = 142 | issue = 2 | pages = 105–106 | date = February 2012 | pmid = 22189042 | doi = 10.1016/j.clim.2011.11.009 }}{{cite journal | vauthors = Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA | title = Current Diagnosis and Management of Small-Cell Lung Cancer | journal = Mayo Clinic Proceedings | volume = 94 | issue = 8 | pages = 1599–1622 | date = August 2019 | pmid = 31378235 | doi = 10.1016/j.mayocp.2019.01.034 | doi-access = free }} [23] => [24] => Cell-based immunotherapies are effective for some cancers.{{cite journal | vauthors = Riley RS, June CH, Langer R, Mitchell MJ | title = Delivery technologies for cancer immunotherapy | journal = Nature Reviews. Drug Discovery | volume = 18 | issue = 3 | pages = 175–196 | date = March 2019 | pmid = 30622344 | pmc = 6410566 | doi = 10.1038/s41573-018-0006-z }}{{Cite journal | vauthors = Li Y, McBride DW, Tang Y, Doycheva D, Zhang JH, Tang Z |date= September 2023 |title=Immunotherapy as a treatment for Stroke: Utilizing regulatory T cells |journal=Brain Hemorrhages |volume=4 |issue=3 |pages=147–153 |doi=10.1016/j.hest.2023.02.003 |issn=2589-238X|doi-access=free }} Immune effector cells such as [[lymphocyte]]s, [[macrophage]]s, [[dendritic cell]]s, [[natural killer cell]]s, and [[Cytotoxic T cell|cytotoxic T lymphocytes]] work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of tumor cells. Vaccine-induced immunity to COVID-19 relies mostly on an immunomodulatory T-cell response.{{cite journal | vauthors = Geers D, Shamier MC, Bogers S, den Hartog G, Gommers L, Nieuwkoop NN, Schmitz KS, Rijsbergen LC, van Osch JA, Dijkhuizen E, Smits G, Comvalius A, van Mourik D, Caniels TG, van Gils MJ, Sanders RW, Oude Munnink BB, Molenkamp R, de Jager HJ, Haagmans BL, de Swart RL, Koopmans MP, van Binnendijk RS, de Vries RD, GeurtsvanKessel CH | display-authors = 6 | title = SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees | journal = Science Immunology | volume = 6 | issue = 59 | pages = eabj1750 | date = May 2021 | pmid = 34035118 | pmc = 9268159 | doi = 10.1126/sciimmunol.abj1750 | doi-access = free }} [25] => [26] => Therapies such as [[granulocyte colony-stimulating factor]] (G-CSF), [[interferon]]s, [[imiquimod]] and cellular membrane fractions from [[bacteria]] are licensed for medical use. Others including [[Interleukin-2|IL-2]], [[Interleukin-7|IL-7]], [[Interleukin 12|IL-12]], various [[chemokine]]s, synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and [[glucan]]s are involved in clinical and preclinical studies. [27] => {{toclimit|3}} [28] => [29] => ==Immunomodulators== [30] => Immunomodulators are the active agents of immunotherapy. They are a diverse array of recombinant, synthetic, and natural preparations.{{cite journal | vauthors = Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN | title = Pharmaco-Immunomodulatory Therapy in COVID-19 | journal = Drugs | volume = 80 | issue = 13 | pages = 1267–1292 | date = September 2020 | pmid = 32696108 | pmc = 7372203 | doi = 10.1007/s40265-020-01367-z | doi-access = free }} [31] => {| class="wikitable sortable" style="text-align:center" [32] => ! Class !! Example agents [33] => |- [34] => | [[Interleukins]] || [[Interleukin 2|IL-2]], [[Interleukin 7|IL-7]], [[Interleukin 12|IL-12]] [35] => |- [36] => | [[Cytokines]] || [[Interferon]]s, [[G-CSF]] [37] => |- [38] => | [[Chemokines]] || [[CCL3]], [[CCL26]], [[CXCL7]] [39] => |- [[Antimicrobial peptides]] || [40] => | [[Immunomodulatory imide drug]]s (IMiDs) || [[thalidomide]] and its analogues ([[lenalidomide]], [[pomalidomide]], and [[apremilast]]), BCG vaccine,{{Cite web|title=Immunomodulators and Their Side Effects|url=https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immunomodulators.html|access-date=2021-06-06|website=www.cancer.org|archive-date=2023-04-08|archive-url=https://web.archive.org/web/20230408092831/https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immunomodulators.html|url-status=live}}{{cite journal | vauthors = Martino A, Casetti R, Poccia F | title = Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs | journal = Vaccine | volume = 25 | issue = 6 | pages = 1023–1029 | date = January 2007 | pmid = 17118497 | doi = 10.1016/j.vaccine.2006.09.070 }} & Covid vaccines{{cite journal | vauthors = Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, Baum A, Pascal K, Quandt J, Maurus D, Brachtendorf S, Lörks V, Sikorski J, Hilker R, Becker D, Eller AK, Grützner J, Boesler C, Rosenbaum C, Kühnle MC, Luxemburger U, Kemmer-Brück A, Langer D, Bexon M, Bolte S, Karikó K, Palanche T, Fischer B, Schultz A, Shi PY, Fontes-Garfias C, Perez JL, Swanson KA, Loschko J, Scully IL, Cutler M, Kalina W, Kyratsous CA, Cooper D, Dormitzer PR, Jansen KU, Türeci Ö | display-authors = 6 | title = COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses | journal = Nature | volume = 586 | issue = 7830 | pages = 594–599 | date = October 2020 | pmid = 32998157 | doi = 10.1038/s41586-020-2814-7 | doi-access = free | bibcode = 2020Natur.586..594S }}{{cite journal | vauthors = Woldemeskel BA, Garliss CC, Blankson JN | title = SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63 | journal = The Journal of Clinical Investigation | volume = 131 | issue = 10 | date = May 2021 | pmid = 33822770 | pmc = 8121504 | doi = 10.1172/JCI149335 }} [41] => |- [42] => | Other || cytosine phosphate-guanosine, oligodeoxynucleotides, [[glucans]] [43] => |} [44] => [45] => ==Activation immunotherapies== [46] => [47] => ===Cancer=== [48] => {{main|Cancer immunotherapy}} [49] => [50] => Cancer treatment used to be focused on killing or removing cancer cells and tumours, with chemotherapy or surgery or radiation. These treatments can be very effective and in many cases are still used. In 2018 the [[Nobel Prize]] in Physiology or Medicine was awarded to [[James P. Allison]] and [[Tasuku Honjo]] "for their discovery of cancer therapy by inhibition of negative immune regulation." Cancer immunotherapy attempts to stimulate the [[immune system]] to destroy tumours. A variety of strategies are in use or are undergoing research and testing. Randomized controlled studies in different cancers resulting in significant increase in survival and disease free period have been reported and its efficacy is enhanced by 20–30% when cell-based immunotherapy is combined with conventional treatment methods. [51] => [52] => One of the oldest forms of cancer immunotherapy is the use of [[BCG vaccine]], which was originally to vaccinate against [[tuberculosis]] and later was found to be useful in the treatment of [[bladder cancer]].{{cite journal | vauthors = Fuge O, [[Neil Vasdev|Vasdev N]], Allchorne P, Green JS | title = Immunotherapy for bladder cancer | journal = Research and Reports in Urology | volume = 7 | pages = 65–79 | date = 2015 | pmid = 26000263 | pmc = 4427258 | doi = 10.2147/RRU.S63447 | doi-access = free }} BCG immunotherapy induces both local and systemic immune responses. The mechanisms by which BCG immunotherapy mediates tumor immunity have been widely studied, but they are still not completely understood.{{cite journal | vauthors = Pettenati C, Ingersoll MA | title = Mechanisms of BCG immunotherapy and its outlook for bladder cancer | journal = Nature Reviews. Urology | volume = 15 | issue = 10 | pages = 615–625 | date = October 2018 | pmid = 29991725 | doi = 10.1038/s41585-018-0055-4 | s2cid = 49670901 }} [53] => [54] => The use of [[monoclonal antibody|monoclonal antibodies]] in cancer therapy was first introduced in 1997 with [[rituximab]], an anti-CD20 antibody for treatment of B cell lymphoma.{{cite journal | vauthors = Salles G, Barrett M, Foà R, Maurer J, O'Brien S, Valente N, Wenger M, Maloney DG | display-authors = 6 | title = Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience | journal = Advances in Therapy | volume = 34 | issue = 10 | pages = 2232–2273 | date = October 2017 | pmid = 28983798 | pmc = 5656728 | doi = 10.1007/s12325-017-0612-x | doi-access = free }} Since then several monoclonal antibodies have been approved for treatment of various haematological malignancies as well as for solid tumours.{{cite journal | vauthors = Hoos A | title = Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations | journal = Nature Reviews. Drug Discovery | volume = 15 | issue = 4 | pages = 235–247 | date = April 2016 | pmid = 26965203 | doi = 10.1038/nrd.2015.35 | s2cid = 54550859 }}{{cite journal | vauthors = Pento JT | title = Monoclonal Antibodies for the Treatment of Cancer | journal = Anticancer Research | volume = 37 | issue = 11 | pages = 5935–5939 | date = November 2017 | pmid = 29061772 | doi = 10.21873/anticanres.12040 | doi-access = free | pmc = 3288558 }} [55] => [56] => The extraction of [[Granulocyte colony-stimulating factor|G-CSF]] [[lymphocytes]] from the blood and expanding in vitro against a tumour antigen before reinjecting the cells with appropriate stimulatory [[cytokines]]. The cells then destroy the tumour cells that express the [[antigen]].{{cite journal | vauthors = Simpson RJ, Bigley AB, Agha N, Hanley PJ, Bollard CM | title = Mobilizing Immune Cells With Exercise for Cancer Immunotherapy | journal = Exercise and Sport Sciences Reviews | volume = 45 | issue = 3 | pages = 163–172 | date = July 2017 | pmid = 28418996 | pmc = 6814300 | doi = 10.1249/JES.0000000000000114 }} Topical immunotherapy utilizes an immune enhancement cream ([[imiquimod]]) which produces [[interferon]], causing the recipient's killer [[T cells]] to destroy [[wart]]s,{{cite journal | vauthors = van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, Kagie MJ, Meijer CJ, Aaronson NK, Kleinjan A, Heijmans-Antonissen C, Zijlstra FJ, Burger MP, Helmerhorst TJ | display-authors = 6 | title = Treatment of vulvar intraepithelial neoplasia with topical imiquimod | journal = The New England Journal of Medicine | volume = 358 | issue = 14 | pages = 1465–1473 | date = April 2008 | pmid = 18385498 | doi = 10.1056/NEJMoa072685 | doi-access = free }} [[actinic keratoses]], [[basal cell cancer]], [[vaginal intraepithelial neoplasia]],{{cite journal | vauthors = Buck HW, Guth KJ | title = Treatment of vaginal intraepithelial neoplasia (primarily low grade) with imiquimod 5% cream | journal = Journal of Lower Genital Tract Disease | volume = 7 | issue = 4 | pages = 290–293 | date = October 2003 | pmid = 17051086 | doi = 10.1097/00128360-200310000-00011 | s2cid = 44649376 }} squamous cell cancer,{{cite journal | vauthors = Järvinen R, Kaasinen E, Sankila A, Rintala E | title = Long-term efficacy of maintenance bacillus Calmette-Guérin versus maintenance mitomycin C instillation therapy in frequently recurrent TaT1 tumours without carcinoma in situ: a subgroup analysis of the prospective, randomised FinnBladder I study with a 20-year follow-up | journal = European Urology | volume = 56 | issue = 2 | pages = 260–265 | date = August 2009 | pmid = 19395154 | doi = 10.1016/j.eururo.2009.04.009 }}{{cite journal | vauthors = Davidson HC, Leibowitz MS, Lopez-Albaitero A, Ferris RL | title = Immunotherapy for head and neck cancer | journal = Oral Oncology | volume = 45 | issue = 9 | pages = 747–751 | date = September 2009 | pmid = 19442565 | doi = 10.1016/j.oraloncology.2009.02.009 | pmc = 8978306 }} cutaneous lymphoma,{{cite journal | vauthors = Dani T, Knobler R | title = Extracorporeal photoimmunotherapy-photopheresis | journal = Frontiers in Bioscience | volume = 14 | issue = 14 | pages = 4769–4777 | date = January 2009 | pmid = 19273388 | doi = 10.2741/3566 | doi-access = free }} and superficial malignant melanoma.{{cite journal | vauthors = Eggermont AM, Schadendorf D | title = Melanoma and immunotherapy | journal = Hematology/Oncology Clinics of North America | volume = 23 | issue = 3 | pages = 547–64, ix-x | date = June 2009 | pmid = 19464602 | doi = 10.1016/j.hoc.2009.03.009 }} Injection immunotherapy ("intralesional" or "intratumoural") uses mumps, candida, the HPV vaccine{{cite journal | vauthors = Chuang CM, Monie A, Wu A, Hung CF | title = Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects | journal = Journal of Biomedical Science | volume = 16 | issue = 1 | pages = 49 | date = May 2009 | pmid = 19473507 | pmc = 2705346 | doi = 10.1186/1423-0127-16-49 | doi-access = free }}{{cite journal | vauthors = Pawlita M, Gissmann L | title = [Recurrent respiratory papillomatosis: indication for HPV vaccination?] | language = de | journal = Deutsche Medizinische Wochenschrift | volume = 134 | pages = S100–S102 | date = April 2009 | issue = Suppl 2 | pmid = 19353471 | doi = 10.1055/s-0029-1220219 | s2cid = 206295083 }} or [[trichophytin]] [[antigen]] injections to treat warts (HPV induced tumours). [57] => [58] => [[Adoptive cell transfer]] has been tested on [[Lung cancer|lung]]{{cite journal | vauthors = Kang N, Zhou J, Zhang T, Wang L, Lu F, Cui Y, Cui L, He W | display-authors = 6 | title = Adoptive immunotherapy of lung cancer with immobilized anti-TCRgammadelta antibody-expanded human gammadelta T-cells in peripheral blood | journal = Cancer Biology & Therapy | volume = 8 | issue = 16 | pages = 1540–1549 | date = August 2009 | pmid = 19471115 | doi = 10.4161/cbt.8.16.8950 | s2cid = 23222462 | doi-access = }} and other cancers, with greatest success achieved in [[melanoma]]. [59] => [60] => ====Dendritic cell-based pump-priming or vaccination==== [61] => [62] => [[Dendritic cells|Dendritic cells (DC)]] can be stimulated to activate a [[cytotoxic]] response towards an [[antigen]]. Dendritic cells, a type of [[antigen-presenting cell]], are harvested from the person needing the immunotherapy. These cells are then either pulsed with an antigen or tumour lysate or [[Transfection|transfected]] with a [[viral vector]], causing them to display the antigen. Upon transfusion into the person, these activated cells present the antigen to the effector lymphocytes ([[Cytotoxic T cell|CD4+ helper T cells]], cytotoxic [[Cytotoxic T cell|CD8+ T cells]] and [[B cell]]s). This initiates a cytotoxic response against tumour cells expressing the antigen (against which the adaptive response has now been primed). The first FDA-approved cell-based immunotherapy,{{cite journal | vauthors = Cheever MA, Higano CS | title = PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine | journal = Clinical Cancer Research | volume = 17 | issue = 11 | pages = 3520–3526 | date = June 2011 | pmid = 21471425 | doi = 10.1158/1078-0432.CCR-10-3126 | s2cid = 135120 | doi-access = free }} the [[cancer vaccine]] [[Sipuleucel-T]] is one example of this approach.{{cite journal | vauthors = Di Lorenzo G, Buonerba C, Kantoff PW | title = Immunotherapy for the treatment of prostate cancer | journal = Nature Reviews. Clinical Oncology | volume = 8 | issue = 9 | pages = 551–561 | date = May 2011 | pmid = 21606971 | doi = 10.1038/nrclinonc.2011.72 | s2cid = 5337484 }} The Immune Response Corporation{{cite journal | vauthors = | title = Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon | journal = Drugs in R&D | volume = 7 | issue = 3 | pages = 197–201 | date = 2006 | pmid = 16752945 | doi = 10.2165/00126839-200607030-00006 | s2cid = 6427074 }} (IRC) developed this immunotherapy and licensed the technology to Dendreon, which obtained FDA clearance. [63] => [64] => The current approaches for [[Dendritic cells- based cancer vaccines|DC-based vaccination]] are mainly based on antigen loading on ''in vitro''-generated DCs from [[monocyte]]s or [[CD34]]+ cells, activating them with different [[Toll-like receptor|TLR]] ligands, [[cytokine]] combinations, and injecting them back to the patients. The ''in vivo'' targeting approaches comprise administering specific cytokines (e.g., [[FMS-like tyrosine kinase 3 ligand|Flt3L]], [[Granulocyte-macrophage colony-stimulating factor|GM-CSF]]) and targeting the DCs with antibodies to C-type lectin receptors or agonistic antibodies (e.g., anti-[[CD40 (protein)|CD40]]) that are conjugated with antigen of interest. Future approach may target DC subsets based on their specifically expressed [[C-type lectin receptor]]s or [[chemokine receptor]]s. Another potential approach is the generation of genetically engineered DCs from [[induced pluripotent stem cell]]s and use of [[neoantigen]]-loaded DCs for inducing better clinical outcome.{{cite journal | vauthors = Sabado RL, Balan S, Bhardwaj N | title = Dendritic cell-based immunotherapy | journal = Cell Research | volume = 27 | issue = 1 | pages = 74–95 | date = January 2017 | pmid = 28025976 | pmc = 5223236 | doi = 10.1038/cr.2016.157 }} [65] => [66] => ====T-cell adoptive transfer==== [67] => [[Adoptive cell transfer]] ''[[in vitro]]'' cultivates autologous, extracted T cells for later transfusion.{{cite journal | vauthors = Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME | title = Adoptive cell transfer: a clinical path to effective cancer immunotherapy | journal = Nature Reviews. Cancer | volume = 8 | issue = 4 | pages = 299–308 | date = April 2008 | pmid = 18354418 | pmc = 2553205 | doi = 10.1038/nrc2355 }} [68] => [69] => Alternatively, [[Genetically engineered T cell]]s are created by harvesting T cells and then infecting the T cells with a [[retrovirus]] that contains a copy of a [[T cell receptor]] (TCR) gene that is specialised to recognise tumour antigens. The virus integrates the receptor into the T cells' [[genome]]. The cells are expanded non-specifically and/or stimulated. The cells are then reinfused and produce an immune response against the tumour cells.{{cite journal | vauthors = Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA | display-authors = 6 | title = Cancer regression in patients after transfer of genetically engineered lymphocytes | journal = Science | volume = 314 | issue = 5796 | pages = 126–129 | date = October 2006 | pmid = 16946036 | pmc = 2267026 | doi = 10.1126/science.1129003 | bibcode = 2006Sci...314..126M }} The technique has been tested on refractory stage IV metastatic melanomas and advanced [[skin cancer]].{{cite journal | vauthors = Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, Jungbluth A, Gnjatic S, Thompson JA, Yee C | display-authors = 6 | title = Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1 | journal = The New England Journal of Medicine | volume = 358 | issue = 25 | pages = 2698–2703 | date = June 2008 | pmid = 18565862 | pmc = 3277288 | doi = 10.1056/NEJMoa0800251 }}{{cite web | url = http://www.cancerresearch.org/events/symposium/cancer-immunology-immunotherapy-2008/program-speakers.html | title = 2008 Symposium Program & Speakers | publisher = Cancer Research Institute | url-status = dead | archive-url = https://web.archive.org/web/20081015045915/http://www.cancerresearch.org/events/symposium/cancer-immunology-immunotherapy-2008/program-speakers.html | archive-date = 2008-10-15 }}{{cite news | vauthors = Highfield R | title = Cancer patient recovers after injection of immune cells | url = https://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/06/18/scicanc118.xml | archive-url = https://web.archive.org/web/20080912063314/http://www.telegraph.co.uk/earth/main.jhtml?xml=%2Fearth%2F2008%2F06%2F18%2Fscicanc118.xml | archive-date = 12 September 2008 | url-status = dead | date = 18 June 2008 | newspaper = The Telegraph | access-date = 22 December 2019 }} The first FDA-approved CAR-T drug, Kymriah, used this approach. To obtain the clinical and commercial supply of this CAR-T, Novartis purchased the manufacturing plant, the distribution system and hired the production team that produced Sipuleucel-T developed by Dendreon and the Immune Response Corporation.{{Cite news|title=Updated: Novartis buys Dendreon New Jersey plant|url=https://www.fiercepharma.com/supply-chain/updated-novartis-buys-dendreon-new-jersey-plant|access-date=2021-12-09|newspaper=Fierce Pharma|date=20 December 2012|language=en|archive-date=2023-06-07|archive-url=https://web.archive.org/web/20230607102450/https://www.fiercepharma.com/supply-chain/updated-novartis-buys-dendreon-new-jersey-plant|url-status=live}} [70] => [71] => Whether T cells are genetically engineered or not, before re-infusion, lympho-depletion of the recipient is required to eliminate regulatory T cells as well as unmodified, endogenous lymphocytes that compete with the transferred cells for homeostatic cytokines.{{cite journal | vauthors = Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, Palmer DC, Chan CC, Klebanoff CA, Overwijk WW, Rosenberg SA, Restifo NP | display-authors = 6 | title = CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells | journal = Journal of Immunology | volume = 174 | issue = 5 | pages = 2591–2601 | date = March 2005 | pmid = 15728465 | pmc = 1403291 | doi = 10.4049/jimmunol.174.5.2591 }}{{cite journal | vauthors = Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, Hwang LN, Yu Z, Wrzesinski C, Heimann DM, Surh CD, Rosenberg SA, Restifo NP | display-authors = 6 | title = Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells | journal = The Journal of Experimental Medicine | volume = 202 | issue = 7 | pages = 907–912 | date = October 2005 | pmid = 16203864 | pmc = 1397916 | doi = 10.1084/jem.20050732 }}{{cite journal | vauthors = Dummer W, Niethammer AG, Baccala R, Lawson BR, Wagner N, Reisfeld RA, Theofilopoulos AN | title = T cell homeostatic proliferation elicits effective antitumor autoimmunity | journal = The Journal of Clinical Investigation | volume = 110 | issue = 2 | pages = 185–192 | date = July 2002 | pmid = 12122110 | pmc = 151053 | doi = 10.1172/JCI15175 }} Lymphodepletion may be achieved by [[Hematopoietic stem cell transplantation#Myeloablative|myeloablative]] chemotherapy, to which total body irradiation may be added for greater effect.{{cite journal | vauthors = Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA | display-authors = 6 | title = Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens | journal = Journal of Clinical Oncology | volume = 26 | issue = 32 | pages = 5233–5239 | date = November 2008 | pmid = 18809613 | pmc = 2652090 | doi = 10.1200/JCO.2008.16.5449 }} Transferred cells multiplied ''in vivo'' and persisted in peripheral blood in many people, sometimes representing levels of 75% of all CD8+ T cells at 6–12 months after infusion.{{cite journal | vauthors = Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA | display-authors = 6 | title = Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes | journal = Science | volume = 298 | issue = 5594 | pages = 850–854 | date = October 2002 | pmid = 12242449 | pmc = 1764179 | doi = 10.1126/science.1076514 | bibcode = 2002Sci...298..850D }} {{As of|2012}}, clinical trials for metastatic melanoma were ongoing at multiple sites.{{cite journal | vauthors = Pilon-Thomas S, Kuhn L, Ellwanger S, Janssen W, Royster E, Marzban S, Kudchadkar R, Zager J, Gibney G, Sondak VK, Weber J, Mulé JJ, Sarnaik AA | display-authors = 6 | title = Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma | journal = Journal of Immunotherapy | volume = 35 | issue = 8 | pages = 615–620 | date = October 2012 | pmid = 22996367 | pmc = 4467830 | doi = 10.1097/CJI.0b013e31826e8f5f }} Clinical responses to adoptive transfer of T cells were observed in patients with metastatic melanoma resistant to multiple immunotherapies.{{cite journal | vauthors = Andersen R, Borch TH, Draghi A, Gokuldass A, Rana MA, Pedersen M, Nielsen M, Kongsted P, Kjeldsen JW, Westergaard MC, Radic HD, Chamberlain CA, Hölmich LR, Hendel HW, Larsen MS, Met Ö, Svane IM, Donia M | display-authors = 6 | title = T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression | journal = Annals of Oncology | volume = 29 | issue = 7 | pages = 1575–1581 | date = July 2018 | pmid = 29688262 | doi = 10.1093/annonc/mdy139 | doi-access = free }} [72] => [73] => ==== Checkpoint inhibitors ==== [74] => {{Main|Checkpoint inhibitor}} [75] => [[PD-1 and PD-L1 inhibitors|Anti-PD-1/PD-L1]] and anti-CTLA-4 antibodies are the two types of checkpoint inhibitors currently available to patients. The approval of anti-cytotoxic T-lymphocyte-associated protein 4 ([[CTLA-4]]) and anti-programmed cell death protein 1 ([[Programmed cell death protein 1|PD-1]]) antibodies for human use has already resulted in significant improvements in disease outcomes for various cancers.{{cite journal | vauthors = Seidel JA, Otsuka A, Kabashima K | title = Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations | journal = Frontiers in Oncology | volume = 8 | pages = 86 | date = 2018-03-28 | pmid = 29644214 | pmc = 5883082 | doi = 10.3389/fonc.2018.00086 | doi-access = free }} [76] => [77] => Although these molecules were originally discovered as molecules playing a role in [[T cell activation]] or [[apoptosis]], subsequent preclinical research showed their important role in the maintenance of peripheral immune tolerance.{{cite journal | vauthors = Haanen JB, Robert C | title = Immune Checkpoint Inhibitors | volume = 42 | pages = 55–66 | date = 2015 | pmid = 26382943 | doi = 10.1159/000437178 | isbn = 978-3-318-05589-4 | journal = Progress in Tumor Research }} [78] => [79] => Immune checkpoint inhibitors are approved to treat some patients with a variety of cancer types, including melanoma, [[breast cancer]], [[bladder cancer]], [[cervical cancer]], [[Colorectal cancer|colon cancer]], [[head and neck cancer]], or [[Hodgkin lymphoma]].{{Cite web|date=2019-09-24|title=Immune Checkpoint Inhibitors - National Cancer Institute|url=https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors|access-date=2020-08-24|website=National Cancer Institute|archive-date=2023-10-22|archive-url=https://web.archive.org/web/20231022075124/https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors|url-status=live}} [80] => [81] => These therapies have revolutionized [[cancer immunotherapy]] as they showed for the first time in many years of research in metastatic [[melanoma]], which is considered one of the most [[Immunogenicity|immunogenic]] human cancers, an improvement in overall survival, with an increasing group of patients benefiting long-term from these treatments. [82] => [83] => ==Immune enhancement therapy== [84] => [[Autologous immune enhancement therapy]] use a person's own peripheral blood-derived [[natural killer cell]]s, cytotoxic T lymphocytes, epithelial cells and other relevant immune cells are expanded ''in vitro'' and then re-infused.{{cite journal | vauthors = Manjunath SR, Ramanan G, Dedeepiya VD, Terunuma H, Deng X, Baskar S, Senthilkumar R, Thamaraikannan P, Srinivasan T, Preethy S, Abraham SJ | display-authors = 6 | title = Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: a case report | journal = Case Reports in Oncology | volume = 5 | issue = 1 | pages = 114–118 | date = January 2012 | pmid = 22666198 | pmc = 3364094 | doi = 10.1159/000337319 }} The therapy has been tested against [[hepatitis C]],{{cite journal | vauthors = Li Y, Zhang T, Ho C, Orange JS, Douglas SD, Ho WZ | title = Natural killer cells inhibit hepatitis C virus expression | journal = Journal of Leukocyte Biology | volume = 76 | issue = 6 | pages = 1171–1179 | date = December 2004 | pmid = 15339939 | doi = 10.1189/jlb.0604372 | doi-access = free }}{{cite journal | vauthors = Doskali M, Tanaka Y, Ohira M, Ishiyama K, Tashiro H, Chayama K, Ohdan H | title = Possibility of adoptive immunotherapy with peripheral blood-derived CD3−CD56+ and CD3+CD56+ cells for inducing antihepatocellular carcinoma and antihepatitis C virus activity | journal = Journal of Immunotherapy | volume = 34 | issue = 2 | pages = 129–138 | date = March 2011 | pmid = 21304407 | doi = 10.1097/CJI.0b013e3182048c4e | s2cid = 26385818 }}{{cite journal | vauthors = Terunuma H, Deng X, Dewan Z, Fujimoto S, Yamamoto N | title = Potential role of NK cells in the induction of immune responses: implications for NK cell-based immunotherapy for cancers and viral infections | journal = International Reviews of Immunology | volume = 27 | issue = 3 | pages = 93–110 | year = 2008 | pmid = 18437601 | doi = 10.1080/08830180801911743 | s2cid = 27557213 }} [[chronic fatigue syndrome]]{{cite journal | vauthors = See DM, Tilles JG | title = alpha-Interferon treatment of patients with chronic fatigue syndrome | journal = Immunological Investigations | volume = 25 | issue = 1–2 | pages = 153–164 | year = 1996 | pmid = 8675231 | doi = 10.3109/08820139609059298 }}{{cite journal | vauthors = Ojo-Amaize EA, Conley EJ, Peter JB | title = Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome | journal = Clinical Infectious Diseases | volume = 18 | pages = S157–S159 | date = January 1994 | issue = Suppl 1 | pmid = 8148445 | doi = 10.1093/clinids/18.Supplement_1.S157 }} and [[HHV6]] infection.{{cite journal | vauthors = Kida K, Isozumi R, Ito M | title = Killing of human Herpes virus 6-infected cells by lymphocytes cultured with interleukin-2 or -12 | journal = Pediatrics International | volume = 42 | issue = 6 | pages = 631–636 | date = December 2000 | pmid = 11192519 | doi = 10.1046/j.1442-200x.2000.01315.x | s2cid = 11297558 }} [85] => [86] => ==Suppression immunotherapies== [87] => [88] => [[Immune suppression]] dampens an abnormal [[immune response]] in [[autoimmune diseases]] or reduces a normal [[immune response]] to prevent [[transplant rejection|rejection]] of [[Organ transplant|transplanted]] organs or cells. [89] => [90] => ===Immunosuppressive drugs=== [91] => [[Immunosuppressive drug]]s help manage organ transplantation and autoimmune disease. Immune responses depend on lymphocyte proliferation. [[Immunosuppressive drug#Cytostatics|Cytostatic drugs]] are immunosuppressive. [[Immunosuppressive drug#Glucocorticoids|Glucocorticoids]] are somewhat more specific inhibitors of lymphocyte activation, whereas inhibitors of [[Immunosuppressive drug#Drugs acting on immunophilins|immunophilins]] more specifically target T lymphocyte activation. [[Immunosuppressive drug#Antibodies|Immunosuppressive antibodies]] target steps in the immune response. [[Immunosuppressive drug#Other drugs|Other drugs]] modulate immune responses and can be used to induce immune regulation. It has been observed in a preclinical trial that regulation of the immune system by small immunosuppressive molecules such as [[vitamin D]], [[dexamethasone]], and [[curcumin]] administered under a low-dose regimen and subcutaneously, could be helpful in preventing or treating chronic inflammation.{{cite journal | vauthors = Ospina-Quintero L, Jaramillo JC, Tabares-Guevara JH, Ramírez-Pineda JR | title = Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice | journal = Frontiers in Immunology | volume = 11 | pages = 743 | date = 24 April 2020 | pmid = 32395119 | pmc = 7197409 | doi = 10.3389/fimmu.2020.00743 | doi-access = free }}{{cite journal | vauthors = Tabares-Guevara JH, Jaramillo JC, Ospina-Quintero L, Piedrahíta-Ochoa CA, García-Valencia N, Bautista-Erazo DE, Caro-Gómez E, Covián C, Retamal-Díaz A, Duarte LF, González PA, Bueno SM, Riedel CA, Kalergis AM, Ramírez-Pineda JR | display-authors = 6 | title = IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule | journal = Frontiers in Immunology | volume = 12 | pages = 708955 | date = 8 July 2021 | pmid = 34305950 | pmc = 8297659 | doi = 10.3389/fimmu.2021.708955 | doi-access = free }} [92] => [93] => ===Immune tolerance=== [94] => [95] => The body naturally does not launch an immune system attack on its own tissues. Models generally identify [[T cell|CD4+ T-cells]] at the centre of the [[autoimmune response]]. Loss of T-cell tolerance then unleashes B-cells and other immune effector cells on to the target tissue. The ideal [[tolerogenic therapy]] would target the specific T-cell clones co-ordinating the autoimmune attack.{{cite journal | vauthors = Rayner F, Isaacs JD | title = Therapeutic tolerance in autoimmune disease | journal = Seminars in Arthritis and Rheumatism | volume = 48 | issue = 3 | pages = 558–562 | date = December 2018 | pmid = 30348449 | doi = 10.1016/j.semarthrit.2018.09.008 | s2cid = 53034800 }} [96] => [97] => [[Immune tolerance]] therapies seek to reset the immune system so that the body stops mistakenly attacking its own organs or cells in [[autoimmune disease]] or accepts foreign tissue in [[organ transplant]]ation.{{cite journal | vauthors = Rotrosen D, Matthews JB, Bluestone JA | title = The immune tolerance network: a new paradigm for developing tolerance-inducing therapies | journal = The Journal of Allergy and Clinical Immunology | volume = 110 | issue = 1 | pages = 17–23 | date = July 2002 | pmid = 12110811 | doi = 10.1067/mai.2002.124258 | s2cid = 30884739 | doi-access = free }} A recent{{when|date=June 2021}} therapeutic approach is the infusion of [[Regulatory T cell|regulatory immune cells]] into transplant recipients. The transfer of regulatory immune cells has the potential to inhibit the activity of effector.{{cite book |vauthors=Stolp J, Zaitsu M, Wood KJ |title=Immunological Tolerance|chapter=Immune Tolerance and Rejection in Organ Transplantation|date=2019|series=Methods in Molecular Biology|volume=1899|pages=159–180|doi=10.1007/978-1-4939-8938-6_12|pmid=30649772 |isbn=978-1-4939-8936-2|s2cid=58542057}}{{cite journal | vauthors = McMurchy AN, Bushell A, Levings MK, Wood KJ | title = Moving to tolerance: clinical application of T regulatory cells | journal = Seminars in Immunology | volume = 23 | issue = 4 | pages = 304–313 | date = August 2011 | pmid = 21620722 | pmc = 3836227 | doi = 10.1016/j.smim.2011.04.001 | series = Advances in Transplantation }} [98] => [99] => Creating [[immune tolerance]] reduces or eliminates the need for lifelong immunosuppression and attendant side effects. It has been tested on transplantations, [[rheumatoid arthritis]], [[type 1 diabetes]] and other autoimmune disorders. [100] => {| class="wikitable" [101] => |+Approaches to therapeutic tolerance induction{{cite journal | vauthors = Baker KF, Isaacs JD | title = Prospects for therapeutic tolerance in humans | journal = Current Opinion in Rheumatology | volume = 26 | issue = 2 | pages = 219–227 | date = March 2014 | pmid = 24378931 | pmc = 4640179 | doi = 10.1097/BOR.0000000000000029 }}{{cite journal | vauthors = Cooles FA, Isaacs JD | title = Treating to re-establish tolerance in inflammatory arthritis - lessons from other diseases | journal = Best Practice & Research. Clinical Rheumatology | volume = 24 | issue = 4 | pages = 497–511 | date = August 2010 | pmid = 20732648 | doi = 10.1016/j.berh.2010.01.007 | series = Pharmacotherapy: Concepts of Pathogenesis and Emerging Treatments }} [102] => ! [103] => !'''Modality''' [104] => !'''Details''' [105] => ! [106] => |- [107] => |'''Non-antigen specific''' [108] => |Monoclonal Antibodies [109] => | [110] => Depleting: [111] => * Anti-[[CD52]] [112] => * Anti-[[CD4]] [113] => * Anti-[[LFA-2]] [114] => | [115] => Non-depleting: [116] => * Anti-CD4 [117] => * Anti-[[CD3 (immunology)|CD3]] [118] => * Anti-[[LFA-1]] [119] => * [[CTLA4]]-Ig [120] => * Anti-[[CD25]] [121] => |- [122] => | [123] => |Haematopoietic stem cell transplantation [124] => |Non-myeloablative [125] => |Myeloablative [126] => |- [127] => | [128] => |Mesenchymal stem cell transplantation [129] => | colspan="2" | [130] => |- [131] => | [132] => |Regulatory T cell therapy [133] => |Non-antigen specific [134] => |Antigen-specific [135] => |- [136] => | [137] => |Low dose [[Interleukin 2|IL-2]] to expand regulatory T cells [138] => | colspan="2" | [139] => |- [140] => | [141] => |Microbiome manipulation [142] => | colspan="2" | [143] => |- [144] => |'''Antigen specific''' [145] => |Peptide therapy [146] => | colspan="2" |Subcutaneous, intradermal, transmucosal (oral, inhaled) [147] => [148] => Tolerogenic dendritic cells, liposomes and nanoparticles [149] => |- [150] => | [151] => |Altered peptide ligands [152] => | [153] => | [154] => |} [155] => [156] => === Allergen Immunotherapy === [157] => {{main|Allergen immunotherapy}} [158] => [159] => Immunotherapy can also be used to treat [[allergy|allergies]]. While allergy treatments (such as [[antihistamine]]s or [[corticosteroids]]) treat allergic symptoms, immunotherapy can reduce sensitivity to [[allergen]]s, lessening its severity. [160] => [161] => Immunotherapy may produce long-term benefits.{{cite journal | vauthors = Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT | display-authors = 6 | title = Long-term clinical efficacy of grass-pollen immunotherapy | journal = The New England Journal of Medicine | volume = 341 | issue = 7 | pages = 468–475 | date = August 1999 | pmid = 10441602 | doi = 10.1056/NEJM199908123410702 | s2cid = 14629112 | doi-access = free }} Immunotherapy is partly effective in some people and ineffective in others, but it offers people with allergies a chance to reduce or stop their symptoms.{{citation needed|date=June 2021}} [162] => [163] => The therapy is indicated for people who are extremely allergic or who cannot avoid specific [[allergen]]s. [164] => [165] => A promising approach to treat food allergies is the use of [[oral immunotherapy]] (OIT). OIT consists in a gradual exposure to increasing amounts of allergen can lead to the majority of subjects tolerating doses of food sufficient to prevent reaction on accidental exposure.{{cite journal | vauthors = MacGinnitie AJ, Rachid R, Gragg H, Little SV, Lakin P, Cianferoni A, Heimall J, Makhija M, Robison R, Chinthrajah RS, Lee J, Lebovidge J, Dominguez T, Rooney C, Lewis MO, Koss J, Burke-Roberts E, Chin K, Logvinenko T, Pongracic JA, Umetsu DT, Spergel J, Nadeau KC, Schneider LC | display-authors = 6 | title = Omalizumab facilitates rapid oral desensitization for peanut allergy | journal = The Journal of Allergy and Clinical Immunology | volume = 139 | issue = 3 | pages = 873–881.e8 | date = March 2017 | pmid = 27609658 | pmc = 5369605 | doi = 10.1016/j.jaci.2016.08.010 | s2cid = 3626708 | doi-access = free }} Dosages increase over time, as the person becomes desensitized. This technique has been tested on infants to prevent peanut allergies.{{Cite web |date=2022-02-07 |title=Oral immunotherapy for peanut allergy in young children |url=https://www.nih.gov/news-events/nih-research-matters/oral-immunotherapy-peanut-allergy-young-children |access-date=2022-06-06 |website=National Institutes of Health (NIH) |language=EN |archive-date=2023-07-12 |archive-url=https://web.archive.org/web/20230712212803/https://www.nih.gov/news-events/nih-research-matters/oral-immunotherapy-peanut-allergy-young-children |url-status=live }} [166] => [167] => ==Helminthic therapies== [168] => [169] => [[Whipworm]] [[Ovum|ova]] (''Trichuris suis'') and [[hookworm]] (''Necator americanus'') have been tested for immunological diseases and allergies, and have proved beneficial on multiple fronts, yet it is not entirely understood. Scientists have found that the immune response triggered by the burrowing of hookworm larvae to pass through the lungs and blood so the production of mast cells and specific antibodies are now present. They also reduce inflammation or responses ties to autoimmune diseases, but despite this, the hookworm's effects are considered to be negative typically.{{Cite web |last=Loukas |first=Alex |title=Immune Response to Hookworm Infections |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC89000/}} [[Helminthic therapy]] has been investigated as a treatment for relapsing remitting [[multiple sclerosis]],{{cite journal | vauthors = Correale J, Farez M | title = Association between parasite infection and immune responses in multiple sclerosis | journal = Annals of Neurology | volume = 61 | issue = 2 | pages = 97–108 | date = February 2007 | pmid = 17230481 | doi = 10.1002/ana.21067 | s2cid = 1033417 }} [[Crohn's disease|Crohn's]],{{cite journal | vauthors = Croese J, O'neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R | title = A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors | journal = Gut | volume = 55 | issue = 1 | pages = 136–137 | date = January 2006 | pmid = 16344586 | pmc = 1856386 | doi = 10.1136/gut.2005.079129 }}{{cite journal | vauthors = Reddy A, Fried B | title = An update on the use of helminths to treat Crohn's and other autoimmunune diseases | journal = Parasitology Research | volume = 104 | issue = 2 | pages = 217–221 | date = January 2009 | pmid = 19050918 | doi = 10.1007/s00436-008-1297-5 | s2cid = 19279688 }}{{cite journal | vauthors = Laclotte C, Oussalah A, Rey P, Bensenane M, Pluvinage N, Chevaux JB, Trouilloud I, Serre AA, Boucekkine T, Bigard MA, Peyrin-Biroulet L | display-authors = 6 | title = [Helminths and inflammatory bowel diseases] | language = fr | journal = Gastroenterologie Clinique et Biologique | volume = 32 | issue = 12 | pages = 1064–1074 | date = December 2008 | pmid = 18619749 | doi = 10.1016/j.gcb.2008.04.030 }} allergies and asthma.{{cite journal | vauthors = Zaccone P, Fehervari Z, Phillips JM, Dunne DW, Cooke A | title = Parasitic worms and inflammatory diseases | journal = Parasite Immunology | volume = 28 | issue = 10 | pages = 515–523 | date = October 2006 | pmid = 16965287 | pmc = 1618732 | doi = 10.1111/j.1365-3024.2006.00879.x }} While there is much to be learned about this, many researchers think that the change in the immune response is thanks to the parasites shifting to a more anti-inflammatory or regulatory system, which would in turn decrease inflammation and self inflicted immune damage as seen in Crohn's and multiple sclerosis. Specifically, MS patients saw lower relapse rates and calmer symptoms in some cases when experimenting with helminthic therapy.{{Cite web |last=Donkers |first=Sarah |date=January–February 2020 |title=Perspectives of People with Multiple Sclerosis about Helminth Immunotherapy |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041615/}} Hypothesized mechanisms include re-polarisation of the [[T helper cell#Th1/Th2 model|Th1 / Th2]] response{{cite journal | vauthors = Brooker S, Bethony J, Hotez PJ | title = Human hookworm infection in the 21st century | journal = Advances in Parasitology | volume = 58 | pages = 197–288 | year = 2004 | pmid = 15603764 | pmc = 2268732 | doi = 10.1016/S0065-308X(04)58004-1 | isbn = 9780120317585 }} and modulation of dendritic cell function.{{cite journal | vauthors = Fujiwara RT, Cançado GG, Freitas PA, Santiago HC, Massara CL, Dos Santos Carvalho O, Corrêa-Oliveira R, Geiger SM, Bethony J | display-authors = 6 | title = Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals | journal = PLOS Neglected Tropical Diseases | volume = 3 | issue = 3 | pages = e399 | year = 2009 | pmid = 19308259 | pmc = 2654967 | doi = 10.1371/journal.pntd.0000399 | doi-access = free }}{{cite journal | vauthors = Carvalho L, Sun J, Kane C, Marshall F, Krawczyk C, Pearce EJ | title = Review series on helminths, immune modulation and the hygiene hypothesis: mechanisms underlying helminth modulation of dendritic cell function | journal = Immunology | volume = 126 | issue = 1 | pages = 28–34 | date = January 2009 | pmid = 19120496 | pmc = 2632707 | doi = 10.1111/j.1365-2567.2008.03008.x }} The helminths downregulate the pro-inflammatory Th1 cytokines, [[interleukin-12]] (IL-12), [[interferon-gamma]] (IFN-γ) and [[Tumour Necrosis Factor|tumor necrosis factor-alpha]] (TNF-α), while promoting the production of regulatory Th2 cytokines such as [[Interleukin 10|IL-10]], [[Interleukin-4|IL-4]], [[Interleukin 5|IL-5]] and [[Interleukin 13|IL-13]].{{cite journal | vauthors = Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, Bresolin N, Sironi M | display-authors = 6 | title = Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions | journal = The Journal of Experimental Medicine | volume = 206 | issue = 6 | pages = 1395–1408 | date = June 2009 | pmid = 19468064 | pmc = 2715056 | doi = 10.1084/jem.20082779 }} [170] => [171] => Co-evolution with helminths has shaped some of the genes associated with [[interleukin]] expression and immunological disorders, such [[Crohn's]], [[ulcerative colitis]] and [[Coeliac disease|celiac disease]]. Helminths' relationship to humans as hosts should be classified as mutualistic or [[symbionts|symbiotic]].{{cite journal | vauthors = Reynolds LA, Finlay BB, Maizels RM | title = Cohabitation in the Intestine: Interactions among Helminth Parasites, Bacterial Microbiota, and Host Immunity | journal = Journal of Immunology | volume = 195 | issue = 9 | pages = 4059–4066 | date = November 2015 | pmid = 26477048 | pmc = 4617609 | doi = 10.4049/jimmunol.1501432 }} In some ways, the relationship is symbiotic because the worms themselves need the host (humans) for survival, because this body supplies them with nutrients and a home. From another perspective, it could be reasoned that it is mutualistic, being that the above information about benefits in autoimmune disorders continues to remain true and supported. Also, some say that the worms can regulate gut bacteria.{{Cite web |last=Loke |first=P'ng |date=June 1, 2016 |title=Helminths and the microbiota: parts of the hygiene hypothesis |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428757/}} Another possibility is one of this being a parasitic relationship, arguing that the possibile rosks of anemia and other disorders outweighs the benefits, yet this is significantly less supported, with the research alluding to the mutualitic and symbiotic approach being much more likely. [172] => [173] => == See also == [174] => * [[Biological response modifier]] [175] => * [[Sepsivac]] [176] => * [[Checkpoint inhibitor]] [177] => * [[Interleukin-2 immunotherapy]] [178] => * [[Immunostimulant]] [179] => * [[Microtransplantation]] [180] => * [[Photoimmunotherapy]] in vitro or in vivo{{cite journal | vauthors = Hong CH, Tang MR, Hsu SH, Yang CH, Tseng CS, Ko YC, Guo CS, Yang CW, Lee SC | display-authors = 6 | title = Enhanced early immune response of leptospiral outer membrane protein LipL32 stimulated by narrow band mid-infrared exposure | journal = Journal of Photochemistry and Photobiology. B, Biology | volume = 198 | pages = 111560 | date = September 2019 | pmid = 31336216 | doi = 10.1016/j.jphotobiol.2019.111560 | s2cid = 198191485 }}{{cite journal | vauthors = Chang HY, Li MH, Huang TC, Hsu CL, Tsai SR, Lee SC, Huang HC, Juan HF | display-authors = 6 | title = Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells | journal = Journal of Proteome Research | volume = 14 | issue = 2 | pages = 1250–1262 | date = February 2015 | pmid = 25556991 | doi = 10.1021/pr5011873 }}{{cite journal | vauthors = Nagaya T, Okuyama S, Ogata F, Maruoka Y, Choyke PL, Kobayashi H | title = Near infrared photoimmunotherapy using a fiber optic diffuser for treating peritoneal gastric cancer dissemination | journal = Gastric Cancer | volume = 22 | issue = 3 | pages = 463–472 | date = May 2019 | pmid = 30171392 | pmc = 7400986 | doi = 10.1007/s10120-018-0871-5 | doi-access = free }}{{cite journal | vauthors = Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H | title = Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules | journal = Nature Medicine | volume = 17 | issue = 12 | pages = 1685–1691 | date = November 2011 | pmid = 22057348 | pmc = 3233641 | doi = 10.1038/nm.2554 }}{{cite journal | vauthors = Sato K, Sato N, Xu B, Nakamura Y, Nagaya T, Choyke PL, Hasegawa Y, Kobayashi H | display-authors = 6 | title = Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy | journal = Science Translational Medicine | volume = 8 | issue = 352 | pages = 352ra110 | date = August 2016 | pmid = 27535621 | pmc = 7780242 | doi = 10.1126/scitranslmed.aaf6843 | doi-access = free }}{{cite journal | vauthors = Nagaya T, Nakamura Y, Sato K, Harada T, Choyke PL, Kobayashi H | title = Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT) | journal = Journal of Controlled Release | volume = 232 | pages = 1–8 | date = June 2016 | pmid = 27059723 | pmc = 4893891 | doi = 10.1016/j.jconrel.2016.04.003 }}{{cite journal | vauthors = Zhen Z, Tang W, Wang M, Zhou S, Wang H, Wu Z, Hao Z, Li Z, Liu L, Xie J | display-authors = 6 | title = Protein Nanocage Mediated Fibroblast-Activation Protein Targeted Photoimmunotherapy To Enhance Cytotoxic T Cell Infiltration and Tumor Control | journal = Nano Letters | volume = 17 | issue = 2 | pages = 862–869 | date = February 2017 | pmid = 28027646 | doi = 10.1021/acs.nanolett.6b04150 | bibcode = 2017NanoL..17..862Z }} [181] => [182] => == References == [183] => {{reflist}} [184] => [185] => == External links == [186] => {{Commons category}} [187] => * {{cite news| vauthors = Langreth R |title=Cancer Miracles|url=https://www.forbes.com/forbes/2009/0302/074_cancer_miracles.html|work=Forbes|date=12 February 2009}} [188] => * [http://www.isbtc.org/about/ International Society for Biological Therapy of Cancer] [189] => * [https://web.archive.org/web/20090125024202/http://cancerresearch.org/programs/meetings/symposium.html Cancer Research Institute Annual International Cancer Immunotherapy Symposia Series] [190] => * [https://www.newscientist.com/article/2201705-the-story-behind-immunotherapys-innovative-cellular-voyage/ The story behind immunotherapy's innovative cellular voyage] [191] => [192] => {{Concepts in infectious disease}} [193] => {{Portal bar|Biology|Medicine}} [194] => {{Authority control}} [195] => [196] => [[Category:Immunotherapy| ]] [197] => [[Category:Virotherapy]] [] => )
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Immunotherapy

Immunotherapy is a form of medical treatment that boosts the body's immune system to fight diseases such as cancer, infections, and autoimmune disorders. It involves the use of various techniques and substances, including antibodies, immune checkpoint inhibitors, and cancer vaccines, to stimulate and enhance the immune response.

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It involves the use of various techniques and substances, including antibodies, immune checkpoint inhibitors, and cancer vaccines, to stimulate and enhance the immune response. By harnessing the power of the immune system, immunotherapy aims to target and destroy abnormal cells while minimizing damage to healthy tissues. The approach has gained significant attention and success in recent years, particularly in the field of cancer treatment. While traditional cancer treatments like chemotherapy and radiation therapy can be effective, they also have severe side effects and often fail to completely eradicate the disease. Immunotherapy offers a more targeted and less toxic alternative, with the potential to produce long-lasting and durable responses. This Wikipedia page provides an overview of the history, types, mechanisms, and applications of immunotherapy, along with the challenges and future prospects of this exciting field of medicine.

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