Immunotherapy Explained

Immunotherapy

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 suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.[1] [2] [3] [4]

Cell-based immunotherapies are effective for some cancers.[5] [6] Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells, and 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.[7]

Therapies such as granulocyte colony-stimulating factor (G-CSF), interferons, imiquimod and cellular membrane fractions from bacteria are licensed for medical use. Others including IL-2, IL-7, IL-12, various chemokines, synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and glucans are involved in clinical and preclinical studies.

Immunomodulators

Immunomodulators are the active agents of immunotherapy. They are a diverse array of recombinant, synthetic, and natural preparations.[8]

Class Example agents
IL-2, IL-7, IL-12
Interferons, G-CSF
CCL3, CCL26, CXCL7
Immunomodulatory imide drugs (IMiDs) thalidomide and its analogues (lenalidomide, pomalidomide, and apremilast), BCG vaccine,[9] [10] & Covid vaccines[11] [12]
Other cytosine phosphate-guanosine, oligodeoxynucleotides, glucans

Activation immunotherapies

Cancer

See main article: Cancer immunotherapy.

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.

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.[13] 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.[14]

The use of monoclonal antibodies in cancer therapy was first introduced in 1997 with rituximab, an anti-CD20 antibody for treatment of B cell lymphoma.[15] Since then several monoclonal antibodies have been approved for treatment of various haematological malignancies as well as for solid tumours.[16] [17]

The extraction of 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.[18] Topical immunotherapy utilizes an immune enhancement cream (imiquimod) which produces interferon, causing the recipient's killer T cells to destroy warts,[19] actinic keratoses, basal cell cancer, vaginal intraepithelial neoplasia,[20] squamous cell cancer,[21] [22] cutaneous lymphoma,[23] and superficial malignant melanoma.[24] Injection immunotherapy ("intralesional" or "intratumoural") uses mumps, candida, the HPV vaccine[25] [26] or trichophytin antigen injections to treat warts (HPV induced tumours).

Adoptive cell transfer has been tested on lung[27] and other cancers, with greatest success achieved in melanoma.

Dendritic cell-based pump-priming or vaccination

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 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 (CD4+ helper T cells, cytotoxic CD8+ T cells and B cells). 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,[28] the cancer vaccine Sipuleucel-T is one example of this approach.[29] The Immune Response Corporation[30] (IRC) developed this immunotherapy and licensed the technology to Dendreon, which obtained FDA clearance.

The current approaches for DC-based vaccination are mainly based on antigen loading on in vitro-generated DCs from monocytes or CD34+ cells, activating them with different TLR ligands, cytokine combinations, and injecting them back to the patients. The in vivo targeting approaches comprise administering specific cytokines (e.g., Flt3L, GM-CSF) and targeting the DCs with antibodies to C-type lectin receptors or agonistic antibodies (e.g., anti-CD40) that are conjugated with antigen of interest. Multiple, next-generation anti-CD40 platforms are being actively developed.[31] Future approach may target DC subsets based on their specifically expressed C-type lectin receptors or chemokine receptors. Another potential approach is the generation of genetically engineered DCs from induced pluripotent stem cells and use of neoantigen-loaded DCs for inducing better clinical outcome.[32]

T-cell adoptive transfer

Adoptive cell transfer in vitro cultivates autologous, extracted T cells for later transfusion.[33]

Alternatively, Genetically engineered T cells 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.[34] The technique has been tested on refractory stage IV metastatic melanomas[33] and advanced skin cancer.[35] [36] [37] 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.[38]

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.[39] [40] [41] Lymphodepletion may be achieved by myeloablative chemotherapy, to which total body irradiation may be added for greater effect.[42] 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.[43], clinical trials for metastatic melanoma were ongoing at multiple sites.[44] Clinical responses to adoptive transfer of T cells were observed in patients with metastatic melanoma resistant to multiple immunotherapies.[45]

Checkpoint inhibitors

See main article: Checkpoint inhibitor. 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 (PD-1) antibodies for human use has already resulted in significant improvements in disease outcomes for various cancers.[46]

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.[47]

Immune checkpoint inhibitors are approved to treat some patients with a variety of cancer types, including melanoma, breast cancer, bladder cancer, cervical cancer, colon cancer, lung cancer head and neck cancer, or Hodgkin lymphoma.[48] [49]

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 immunogenic human cancers, an improvement in overall survival, with an increasing group of patients benefiting long-term from these treatments, although caution remains needed for specific subgroups.[50] [51]

The next generation of checkpoint inhibitors targets other receptors such as lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT). Antibodies against these receptors have been evaluated in clinical studies, but have not yet been approved for widespread use.[52]

Immune enhancement therapy

Autologous immune enhancement therapy use a person's own peripheral blood-derived natural killer cells, cytotoxic T lymphocytes, epithelial cells and other relevant immune cells are expanded in vitro and then re-infused.[53] The therapy has been tested against hepatitis C,[54] [55] [56] chronic fatigue syndrome[57] [58] and HHV6 infection.[59]

Suppression immunotherapies

Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent rejection of transplanted organs or cells.

Immunosuppressive drugs

Immunosuppressive drugs can be used to control the immune system with organ transplantation and with autoimmune disease. Immune responses depend on lymphocyte proliferation. Lymphocyte proliferation is the multiplication of lymphocyte cells used to fight and remember foreign invaders.[60] Cytostatic drugs are a type of immunosuppressive drug that aids in slowing down the growth of rapidly dividing cells. Another example of an immunosuppressive drug is Glucocorticoids which are more specific inhibitors of lymphocyte activation. Glucocorticoids work by emulating actions of natural actions of the body's adrenal glands to help suppress the immune system, which is helpful with autoimmune diseases|,[61] Alternatively, inhibitors of immunophilins more specifically target T lymphocyte activation, the process by which T-lymphocytes stimulate and begin to respond to a specific antigen,[62] There is also Immunosuppressive antibodies which target steps in the immune response to prevent the body from attacking its tissues, which is a problem with autoimmune diseases,[63] There are various other drugs that modulate immune responses and can be used to induce immune regulation. It was observed in a preclinical trial that regulation of the immune system by small immunosuppressive molecules such as vitamin D, dexamethasone, and curcumin could be helpful in preventing or treating chronic inflation. Given that the molecules are administered under a low-dose regimen and subcutaneously. A study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Valrubicin-loaded immunoliposomes (Val-ILs) as a novel nanoparticle technology to target immunosuppressive cells. Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death of immunosuppressive cells. [64]

Immune tolerance

The body naturally does not launch an immune system attack on its own tissues. Models generally identify 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.[65]

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 transplantation.[66] A recent therapeutic approach is the infusion of regulatory immune cells into transplant recipients. The transfer of regulatory immune cells has the potential to inhibit the activity of effector.[67] [68]

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.

Approaches to therapeutic tolerance induction[69] [70] !!Modality!Details!
Non-antigen specificMonoclonal AntibodiesDepleting: Non-depleting:
Haematopoietic stem cell transplantationNon-myeloablativeMyeloablative
Mesenchymal stem cell transplantation
Regulatory T cell therapyNon-antigen specificAntigen-specific
Low dose IL-2 to expand regulatory T cells
Microbiome manipulation
Antigen specificPeptide therapySubcutaneous, intradermal, transmucosal (oral, inhaled)

Tolerogenic dendritic cells, liposomes and nanoparticles

Altered peptide ligands

Allergen immunotherapy

See main article: Allergen immunotherapy.

Immunotherapy can also be used to treat allergies. While allergy treatments (such as antihistamines or corticosteroids) treat allergic symptoms, immunotherapy can reduce sensitivity to allergens, lessening its severity. Allergen immunotherapy can also be referred to as allergen desensitization or hypo-sensitization.[71] Immunotherapy may produce long-term benefits.[72] 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.

Subcutaneous allergen immunotherapy was first introduced in 1911 through the hypothesis that people with hay fever were sensitive to pollen from grass. A process was developed to create an extract by drawing out timothy pollen in distilled water and then boiling it. This was injected into patients in increasing doses to help alleviate symptoms. [73]

Allergen Immunotherapy is indicated for people who are extremely allergic or who cannot avoid specific allergens and when there is evidence of an IgE-mediated reaction that correlates with allergen symptoms. These IgE-mediated reactions can be identified via a blood IgE test or skin testing. If a specific IgE antibody is negative, there is no evidence that allergen immunotherapy will be effective for that patient.

However, there are risks associated with allergen immunotherapy as it is the administration of an agent the patient is known to be highly allergic to. Patients are at increased risk of fatal anaphylaxis, local reaction at the site of injection, or life-threatening systemic allergic reactions.

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.[74] Dosages increase over time, as the person becomes desensitized. This technique has been tested on infants to prevent peanut allergies.[75]

Helminthic therapies

Whipworm 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.[76] Helminthic therapy has been investigated as a treatment for relapsing remitting multiple sclerosis,[77] Crohn's,[78] [79] [80] allergies and asthma.[81] 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.[82] Hypothesized mechanisms include re-polarisation of the Th1 / Th2 response[83] and modulation of dendritic cell function.[84] [85] The helminths downregulate the pro-inflammatory Th1 cytokines, interleukin-12 (IL-12), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), while promoting the production of regulatory Th2 cytokines such as IL-10, IL-4, IL-5 and IL-13.[83] [86]

Co-evolution with helminths has shaped some of the genes associated with interleukin expression and immunological disorders, such Crohn's, ulcerative colitis and celiac disease. Helminths' relationship to humans as hosts should be classified as mutualistic or symbiotic.[87] 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.[88] 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.

See also

External links

Notes and References

  1. Web site: Immunotherapy Memorial Sloan Kettering Cancer Center. mskcc.org. 2017-07-27. 2019-10-19. https://web.archive.org/web/20191019141622/https://www.mskcc.org/cancer-care/diagnosis-treatment/cancer-treatments/immunotherapy. live.
  2. Syn NL, Teng MW, Mok TS, Soo RA . De-novo and acquired resistance to immune checkpoint targeting . The Lancet. Oncology . 18 . 12 . e731–e741 . December 2017 . 29208439 . 10.1016/s1470-2045(17)30607-1 .
  3. Conforti L . The ion channel network in T lymphocytes, a target for immunotherapy . Clinical Immunology . 142 . 2 . 105–106 . February 2012 . 22189042 . 10.1016/j.clim.2011.11.009 .
  4. Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA . Current Diagnosis and Management of Small-Cell Lung Cancer . Mayo Clinic Proceedings . 94 . 8 . 1599–1622 . August 2019 . 31378235 . 10.1016/j.mayocp.2019.01.034 . free .
  5. Riley RS, June CH, Langer R, Mitchell MJ . Delivery technologies for cancer immunotherapy . Nature Reviews. Drug Discovery . 18 . 3 . 175–196 . March 2019 . 30622344 . 6410566 . 10.1038/s41573-018-0006-z .
  6. Li Y, McBride DW, Tang Y, Doycheva D, Zhang JH, Tang Z . September 2023 . Immunotherapy as a treatment for Stroke: Utilizing regulatory T cells . Brain Hemorrhages . 4 . 3 . 147–153 . 10.1016/j.hest.2023.02.003 . 2589-238X. free .
  7. 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 . SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees . Science Immunology . 6 . 59 . eabj1750 . May 2021 . 34035118 . 9268159 . 10.1126/sciimmunol.abj1750 . free .
  8. Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN . Pharmaco-Immunomodulatory Therapy in COVID-19 . Drugs . 80 . 13 . 1267–1292 . September 2020 . 32696108 . 7372203 . 10.1007/s40265-020-01367-z . free .
  9. Web site: Immunomodulators and Their Side Effects. 2021-06-06. www.cancer.org. 2023-04-08. https://web.archive.org/web/20230408092831/https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immunomodulators.html. live.
  10. Martino A, Casetti R, Poccia F . Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs . Vaccine . 25 . 6 . 1023–1029 . January 2007 . 17118497 . 10.1016/j.vaccine.2006.09.070 .
  11. 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 . COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses . Nature . 586 . 7830 . 594–599 . October 2020 . 32998157 . 10.1038/s41586-020-2814-7 . free . 2020Natur.586..594S .
  12. Woldemeskel BA, Garliss CC, Blankson JN . SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63 . The Journal of Clinical Investigation . 131 . 10 . May 2021 . 33822770 . 8121504 . 10.1172/JCI149335 .
  13. Fuge O, Vasdev N, Allchorne P, Green JS . Immunotherapy for bladder cancer . Research and Reports in Urology . 7 . 65–79 . 2015 . 26000263 . 4427258 . 10.2147/RRU.S63447 . free .
  14. Pettenati C, Ingersoll MA . Mechanisms of BCG immunotherapy and its outlook for bladder cancer . Nature Reviews. Urology . 15 . 10 . 615–625 . October 2018 . 29991725 . 10.1038/s41585-018-0055-4 . 49670901 .
  15. Salles G, Barrett M, Foà R, Maurer J, O'Brien S, Valente N, Wenger M, Maloney DG . Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience . Advances in Therapy . 34 . 10 . 2232–2273 . October 2017 . 28983798 . 5656728 . 10.1007/s12325-017-0612-x . free .
  16. Hoos A . Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations . Nature Reviews. Drug Discovery . 15 . 4 . 235–247 . April 2016 . 26965203 . 10.1038/nrd.2015.35 . 54550859 .
  17. Pento JT . Monoclonal Antibodies for the Treatment of Cancer . Anticancer Research . 37 . 11 . 5935–5939 . November 2017 . 29061772 . 10.21873/anticanres.12040 . free . 3288558 .
  18. Simpson RJ, Bigley AB, Agha N, Hanley PJ, Bollard CM . Mobilizing Immune Cells With Exercise for Cancer Immunotherapy . Exercise and Sport Sciences Reviews . 45 . 3 . 163–172 . July 2017 . 28418996 . 6814300 . 10.1249/JES.0000000000000114 .
  19. 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 . Treatment of vulvar intraepithelial neoplasia with topical imiquimod . The New England Journal of Medicine . 358 . 14 . 1465–1473 . April 2008 . 18385498 . 10.1056/NEJMoa072685 . free .
  20. Buck HW, Guth KJ . Treatment of vaginal intraepithelial neoplasia (primarily low grade) with imiquimod 5% cream . Journal of Lower Genital Tract Disease . 7 . 4 . 290–293 . October 2003 . 17051086 . 10.1097/00128360-200310000-00011 . 44649376 .
  21. Järvinen R, Kaasinen E, Sankila A, Rintala E . 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 . European Urology . 56 . 2 . 260–265 . August 2009 . 19395154 . 10.1016/j.eururo.2009.04.009 .
  22. Davidson HC, Leibowitz MS, Lopez-Albaitero A, Ferris RL . Immunotherapy for head and neck cancer . Oral Oncology . 45 . 9 . 747–751 . September 2009 . 19442565 . 10.1016/j.oraloncology.2009.02.009 . 8978306 .
  23. Dani T, Knobler R . Extracorporeal photoimmunotherapy-photopheresis . Frontiers in Bioscience . 14 . 14 . 4769–4777 . January 2009 . 19273388 . 10.2741/3566 . free .
  24. Eggermont AM, Schadendorf D . Melanoma and immunotherapy . Hematology/Oncology Clinics of North America . 23 . 3 . 547–64, ix-x . June 2009 . 19464602 . 10.1016/j.hoc.2009.03.009 .
  25. Chuang CM, Monie A, Wu A, Hung CF . Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects . Journal of Biomedical Science . 16 . 1 . 49 . May 2009 . 19473507 . 2705346 . 10.1186/1423-0127-16-49 . free .
  26. Pawlita M, Gissmann L . [Recurrent respiratory papillomatosis: indication for HPV vaccination?] . de . Deutsche Medizinische Wochenschrift . 134 . S100–S102 . April 2009 . Suppl 2 . 19353471 . 10.1055/s-0029-1220219 . 206295083 .
  27. Kang N, Zhou J, Zhang T, Wang L, Lu F, Cui Y, Cui L, He W . Adoptive immunotherapy of lung cancer with immobilized anti-TCRgammadelta antibody-expanded human gammadelta T-cells in peripheral blood . Cancer Biology & Therapy . 8 . 16 . 1540–1549 . August 2009 . 19471115 . 10.4161/cbt.8.16.8950 . 23222462 .
  28. Cheever MA, Higano CS . PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine . Clinical Cancer Research . 17 . 11 . 3520–3526 . June 2011 . 21471425 . 10.1158/1078-0432.CCR-10-3126 . 135120 . free .
  29. Di Lorenzo G, Buonerba C, Kantoff PW . Immunotherapy for the treatment of prostate cancer . Nature Reviews. Clinical Oncology . 8 . 9 . 551–561 . May 2011 . 21606971 . 10.1038/nrclinonc.2011.72 . 5337484 .
  30. Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon . Drugs in R&D . 7 . 3 . 197–201 . 2006 . 16752945 . 10.2165/00126839-200607030-00006 . 6427074 .
  31. Andersson H, Nyesiga B, Hermodsson T, Enell Smith K, Hägerbrand K, Lindstedt M, Ellmark P . Next-generation CD40 agonists for cancer immunotherapy . Expert Opinion on Biological Therapy . 24 . 5 . 351–363 . May 2024 . 38764393 . 10.1080/14712598.2024.2357714 . free .
  32. Sabado RL, Balan S, Bhardwaj N . Dendritic cell-based immunotherapy . Cell Research . 27 . 1 . 74–95 . January 2017 . 28025976 . 5223236 . 10.1038/cr.2016.157 .
  33. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME . Adoptive cell transfer: a clinical path to effective cancer immunotherapy . Nature Reviews. Cancer . 8 . 4 . 299–308 . April 2008 . 18354418 . 2553205 . 10.1038/nrc2355 .
  34. 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 . Cancer regression in patients after transfer of genetically engineered lymphocytes . Science . 314 . 5796 . 126–129 . October 2006 . 16946036 . 2267026 . 10.1126/science.1129003 . 2006Sci...314..126M .
  35. Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, Jungbluth A, Gnjatic S, Thompson JA, Yee C . Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1 . The New England Journal of Medicine . 358 . 25 . 2698–2703 . June 2008 . 18565862 . 3277288 . 10.1056/NEJMoa0800251 .
  36. Web site: 2008 Symposium Program & Speakers . Cancer Research Institute . dead . https://web.archive.org/web/20081015045915/http://www.cancerresearch.org/events/symposium/cancer-immunology-immunotherapy-2008/program-speakers.html . 2008-10-15 .
  37. News: Highfield R . Cancer patient recovers after injection of immune cells . https://web.archive.org/web/20080912063314/http://www.telegraph.co.uk/earth/main.jhtml?xml=%2Fearth%2F2008%2F06%2F18%2Fscicanc118.xml . 12 September 2008 . dead . 18 June 2008 . The Telegraph . 22 December 2019 .
  38. News: Updated: Novartis buys Dendreon New Jersey plant. 2021-12-09. Fierce Pharma. 20 December 2012. en. 2023-06-07. https://web.archive.org/web/20230607102450/https://www.fiercepharma.com/supply-chain/updated-novartis-buys-dendreon-new-jersey-plant. live.
  39. Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, Palmer DC, Chan CC, Klebanoff CA, Overwijk WW, Rosenberg SA, Restifo NP . 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 of Immunology . 174 . 5 . 2591–2601 . March 2005 . 15728465 . 1403291 . 10.4049/jimmunol.174.5.2591 .
  40. 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 . Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells . The Journal of Experimental Medicine . 202 . 7 . 907–912 . October 2005 . 16203864 . 1397916 . 10.1084/jem.20050732 .
  41. Dummer W, Niethammer AG, Baccala R, Lawson BR, Wagner N, Reisfeld RA, Theofilopoulos AN . T cell homeostatic proliferation elicits effective antitumor autoimmunity . The Journal of Clinical Investigation . 110 . 2 . 185–192 . July 2002 . 12122110 . 151053 . 10.1172/JCI15175 .
  42. 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 . Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens . Journal of Clinical Oncology . 26 . 32 . 5233–5239 . November 2008 . 18809613 . 2652090 . 10.1200/JCO.2008.16.5449 .
  43. 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 . Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes . Science . 298 . 5594 . 850–854 . October 2002 . 12242449 . 1764179 . 10.1126/science.1076514 . 2002Sci...298..850D .
  44. 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 . Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma . Journal of Immunotherapy . 35 . 8 . 615–620 . October 2012 . 22996367 . 4467830 . 10.1097/CJI.0b013e31826e8f5f .
  45. 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 . T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression . Annals of Oncology . 29 . 7 . 1575–1581 . July 2018 . 29688262 . 10.1093/annonc/mdy139 . free .
  46. Seidel JA, Otsuka A, Kabashima K . Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations . Frontiers in Oncology . 8 . 86 . 2018-03-28 . 29644214 . 5883082 . 10.3389/fonc.2018.00086 . free .
  47. Haanen JB, Robert C . Immune Checkpoint Inhibitors . 42 . 55–66 . 2015 . 26382943 . 10.1159/000437178 . 978-3-318-05589-4 . Progress in Tumor Research .
  48. Web site: 2019-09-24. Immune Checkpoint Inhibitors - National Cancer Institute. 2020-08-24. National Cancer Institute. 2023-10-22. https://web.archive.org/web/20231022075124/https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors. live.
  49. Web site: Immunotherapy By Cancer Type . Cancer Research Institute .
  50. Queirolo P, Boutros A, Tanda E, Spagnolo F, Quaglino P . Immune-checkpoint inhibitors for the treatment of metastatic melanoma: a model of cancer immunotherapy . Seminars in Cancer Biology . 59 . 290–297 . December 2019 . 31430555 . 10.1016/j.semcancer.2019.08.001 . 2318/1717353 . free .
  51. Moyers JT, Glitza Oliva IC . Immunotherapy for Melanoma . Advances in Experimental Medicine and Biology . 1342 . 81–111 . 2021 . 34972963 . 10.1007/978-3-030-79308-1_3 .
  52. Cai L, Li Y, Tan J, Xu L, Li Y . Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy . Journal of Hematology & Oncology . 16 . 1 . 101 . September 2023 . 37670328 . 10478462 . 10.1186/s13045-023-01499-1 . free .
  53. Manjunath SR, Ramanan G, Dedeepiya VD, Terunuma H, Deng X, Baskar S, Senthilkumar R, Thamaraikannan P, Srinivasan T, Preethy S, Abraham SJ . Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: a case report . Case Reports in Oncology . 5 . 1 . 114–118 . January 2012 . 22666198 . 3364094 . 10.1159/000337319 .
  54. Li Y, Zhang T, Ho C, Orange JS, Douglas SD, Ho WZ . Natural killer cells inhibit hepatitis C virus expression . Journal of Leukocyte Biology . 76 . 6 . 1171–1179 . December 2004 . 15339939 . 10.1189/jlb.0604372 . free .
  55. Doskali M, Tanaka Y, Ohira M, Ishiyama K, Tashiro H, Chayama K, Ohdan H . Possibility of adoptive immunotherapy with peripheral blood-derived CD3−CD56+ and CD3+CD56+ cells for inducing antihepatocellular carcinoma and antihepatitis C virus activity . Journal of Immunotherapy . 34 . 2 . 129–138 . March 2011 . 21304407 . 10.1097/CJI.0b013e3182048c4e . 26385818 .
  56. Terunuma H, Deng X, Dewan Z, Fujimoto S, Yamamoto N . Potential role of NK cells in the induction of immune responses: implications for NK cell-based immunotherapy for cancers and viral infections . International Reviews of Immunology . 27 . 3 . 93–110 . 2008 . 18437601 . 10.1080/08830180801911743 . 27557213 .
  57. See DM, Tilles JG . alpha-Interferon treatment of patients with chronic fatigue syndrome . Immunological Investigations . 25 . 1–2 . 153–164 . 1996 . 8675231 . 10.3109/08820139609059298 .
  58. Ojo-Amaize EA, Conley EJ, Peter JB . Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome . Clinical Infectious Diseases . 18 . S157–S159 . January 1994 . Suppl 1 . 8148445 . 10.1093/clinids/18.Supplement_1.S157 .
  59. Kida K, Isozumi R, Ito M . Killing of human Herpes virus 6-infected cells by lymphocytes cultured with interleukin-2 or -12 . Pediatrics International . 42 . 6 . 631–636 . December 2000 . 11192519 . 10.1046/j.1442-200x.2000.01315.x . 11297558 .
  60. Web site: Lymphocyte Proliferation - an overview ScienceDirect Topics . 2024-05-10 . www.sciencedirect.com.
  61. Web site: Lymphocyte Proliferation - an overview ScienceDirect Topics . 2024-05-10 . www.sciencedirect.com.
  62. Book: Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P . 2007-12-31 . Molecular Biology of the Cell . 10.1201/9780203833445 . 978-0-203-83344-5 .
  63. Qian Y, Dupps WJ, Meisler DM, Jeng BH . 2010 . Epithelial Debridement for Epithelial Basement Membrane Abnormalities Associated with Endothelial Disorders . European Ophthalmic Review . 04 . 1 . 70 . 10.17925/eor.2010.04.01.70 . 1756-1795.
  64. Georgievski A, Bellaye PS, Tournier B, Choubley H, Pais de Barros JP, Herbst M, Béduneau A, Callier P, Collin B, Végran F, Ballerini P, Garrido C, Quéré R . Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers . Cell Death Dis. 15(5):328 . May 2024 . 15 . 328 . 38734740 . 10.1038/s41419-024-06715-5 . 11088660 .
  65. Rayner F, Isaacs JD . Therapeutic tolerance in autoimmune disease . Seminars in Arthritis and Rheumatism . 48 . 3 . 558–562 . December 2018 . 30348449 . 10.1016/j.semarthrit.2018.09.008 . 53034800 .
  66. Rotrosen D, Matthews JB, Bluestone JA . The immune tolerance network: a new paradigm for developing tolerance-inducing therapies . The Journal of Allergy and Clinical Immunology . 110 . 1 . 17–23 . July 2002 . 12110811 . 10.1067/mai.2002.124258 . 30884739 . free .
  67. Book: Stolp J, Zaitsu M, Wood KJ . Immunological Tolerance. Immune Tolerance and Rejection in Organ Transplantation. 2019. Methods in Molecular Biology. 1899. 159–180. 10.1007/978-1-4939-8938-6_12. 30649772 . 978-1-4939-8936-2. 58542057.
  68. McMurchy AN, Bushell A, Levings MK, Wood KJ . Moving to tolerance: clinical application of T regulatory cells . Seminars in Immunology . 23 . 4 . 304–313 . August 2011 . 21620722 . 3836227 . 10.1016/j.smim.2011.04.001 . Advances in Transplantation .
  69. Baker KF, Isaacs JD . Prospects for therapeutic tolerance in humans . Current Opinion in Rheumatology . 26 . 2 . 219–227 . March 2014 . 24378931 . 4640179 . 10.1097/BOR.0000000000000029 .
  70. Cooles FA, Isaacs JD . Treating to re-establish tolerance in inflammatory arthritis - lessons from other diseases . Best Practice & Research. Clinical Rheumatology . 24 . 4 . 497–511 . August 2010 . 20732648 . 10.1016/j.berh.2010.01.007 . Pharmacotherapy: Concepts of Pathogenesis and Emerging Treatments .
  71. Book: Persaud Y, Memon RJ, Savliwala MN . Allergy Immunotherapy . 2024 . StatPearls . http://www.ncbi.nlm.nih.gov/books/NBK535367/ . 2024-05-10 . Treasure Island (FL) . StatPearls Publishing . 30570988 .
  72. Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT . Long-term clinical efficacy of grass-pollen immunotherapy . The New England Journal of Medicine . 341 . 7 . 468–475 . August 1999 . 10441602 . 10.1056/NEJM199908123410702 . 14629112 . free .
  73. James C, Bernstein DI . February 2017 . Allergen immunotherapy: an updated review of safety . Current Opinion in Allergy & Clinical Immunology . en . 17 . 1 . 55–59 . 10.1097/ACI.0000000000000335 . 27906697 . 5644500 . 1528-4050.
  74. 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 . Omalizumab facilitates rapid oral desensitization for peanut allergy . The Journal of Allergy and Clinical Immunology . 139 . 3 . 873–881.e8 . March 2017 . 27609658 . 5369605 . 10.1016/j.jaci.2016.08.010 . 3626708 . free .
  75. Web site: 2022-02-07 . Oral immunotherapy for peanut allergy in young children . 2022-06-06 . National Institutes of Health (NIH) . EN . 2023-07-12 . https://web.archive.org/web/20230712212803/https://www.nih.gov/news-events/nih-research-matters/oral-immunotherapy-peanut-allergy-young-children . live .
  76. Loukas A, Prociv P . Immune responses in hookworm infections . Clinical Microbiology Reviews . 14 . 4 . 689–703, table of contents . October 2001 . 11585781 . 89000 . 10.1128/CMR.14.4.689-703.2001 .
  77. Correale J, Farez M . Association between parasite infection and immune responses in multiple sclerosis . Annals of Neurology . 61 . 2 . 97–108 . February 2007 . 17230481 . 10.1002/ana.21067 . 1033417 .
  78. Croese J, O'neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R . A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors . Gut . 55 . 1 . 136–137 . January 2006 . 16344586 . 1856386 . 10.1136/gut.2005.079129 .
  79. Reddy A, Fried B . An update on the use of helminths to treat Crohn's and other autoimmunune diseases . Parasitology Research . 104 . 2 . 217–221 . January 2009 . 19050918 . 10.1007/s00436-008-1297-5 . 19279688 .
  80. Laclotte C, Oussalah A, Rey P, Bensenane M, Pluvinage N, Chevaux JB, Trouilloud I, Serre AA, Boucekkine T, Bigard MA, Peyrin-Biroulet L . [Helminths and inflammatory bowel diseases] . fr . Gastroenterologie Clinique et Biologique . 32 . 12 . 1064–1074 . December 2008 . 18619749 . 10.1016/j.gcb.2008.04.030 .
  81. Zaccone P, Fehervari Z, Phillips JM, Dunne DW, Cooke A . Parasitic worms and inflammatory diseases . Parasite Immunology . 28 . 10 . 515–523 . October 2006 . 16965287 . 1618732 . 10.1111/j.1365-3024.2006.00879.x .
  82. Donkers SJ, Kirkland MC, Charabati M, Osborne LC . Perspectives of People with Multiple Sclerosis About Helminth Immunotherapy . International Journal of MS Care . 22 . 1 . 43–51 . 2020 . 32123528 . 7041615 . 10.7224/1537-2073.2019-044 .
  83. Brooker S, Bethony J, Hotez PJ . Human hookworm infection in the 21st century . Advances in Parasitology . 58 . 197–288 . 2004 . 15603764 . 2268732 . 10.1016/S0065-308X(04)58004-1 . 9780120317585 .
  84. Fujiwara RT, Cançado GG, Freitas PA, Santiago HC, Massara CL, Dos Santos Carvalho O, Corrêa-Oliveira R, Geiger SM, Bethony J . Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals . PLOS Neglected Tropical Diseases . 3 . 3 . e399 . 2009 . 19308259 . 2654967 . 10.1371/journal.pntd.0000399 . free .
  85. Carvalho L, Sun J, Kane C, Marshall F, Krawczyk C, Pearce EJ . Review series on helminths, immune modulation and the hygiene hypothesis: mechanisms underlying helminth modulation of dendritic cell function . Immunology . 126 . 1 . 28–34 . January 2009 . 19120496 . 2632707 . 10.1111/j.1365-2567.2008.03008.x .
  86. Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, Bresolin N, Sironi M . Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions . The Journal of Experimental Medicine . 206 . 6 . 1395–1408 . June 2009 . 19468064 . 2715056 . 10.1084/jem.20082779 .
  87. Reynolds LA, Finlay BB, Maizels RM . Cohabitation in the Intestine: Interactions among Helminth Parasites, Bacterial Microbiota, and Host Immunity . Journal of Immunology . 195 . 9 . 4059–4066 . November 2015 . 26477048 . 4617609 . 10.4049/jimmunol.1501432 .
  88. Loke P, Lim YA . Helminths and the microbiota: parts of the hygiene hypothesis . Parasite Immunology . 37 . 6 . 314–23 . June 2015 . 25869420 . 4428757 . 10.1111/pim.12193 .
  89. Hong CH, Tang MR, Hsu SH, Yang CH, Tseng CS, Ko YC, Guo CS, Yang CW, Lee SC . Enhanced early immune response of leptospiral outer membrane protein LipL32 stimulated by narrow band mid-infrared exposure . Journal of Photochemistry and Photobiology. B, Biology . 198 . 111560 . September 2019 . 31336216 . 10.1016/j.jphotobiol.2019.111560 . 2019JPPB..19811560H . 198191485 .
  90. Chang HY, Li MH, Huang TC, Hsu CL, Tsai SR, Lee SC, Huang HC, Juan HF . Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells . Journal of Proteome Research . 14 . 2 . 1250–1262 . February 2015 . 25556991 . 10.1021/pr5011873 .
  91. Nagaya T, Okuyama S, Ogata F, Maruoka Y, Choyke PL, Kobayashi H . Near infrared photoimmunotherapy using a fiber optic diffuser for treating peritoneal gastric cancer dissemination . Gastric Cancer . 22 . 3 . 463–472 . May 2019 . 30171392 . 7400986 . 10.1007/s10120-018-0871-5 . free .
  92. Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H . Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules . Nature Medicine . 17 . 12 . 1685–1691 . November 2011 . 22057348 . 3233641 . 10.1038/nm.2554 .
  93. Sato K, Sato N, Xu B, Nakamura Y, Nagaya T, Choyke PL, Hasegawa Y, Kobayashi H . Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy . Science Translational Medicine . 8 . 352 . 352ra110 . August 2016 . 27535621 . 7780242 . 10.1126/scitranslmed.aaf6843 . free .
  94. Nagaya T, Nakamura Y, Sato K, Harada T, Choyke PL, Kobayashi H . Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT) . Journal of Controlled Release . 232 . 1–8 . June 2016 . 27059723 . 4893891 . 10.1016/j.jconrel.2016.04.003 .
  95. Zhen Z, Tang W, Wang M, Zhou S, Wang H, Wu Z, Hao Z, Li Z, Liu L, Xie J . Protein Nanocage Mediated Fibroblast-Activation Protein Targeted Photoimmunotherapy To Enhance Cytotoxic T Cell Infiltration and Tumor Control . Nano Letters . 17 . 2 . 862–869 . February 2017 . 28027646 . 10.1021/acs.nanolett.6b04150 . 2017NanoL..17..862Z .

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