Langbahn Team – Weltmeisterschaft

Immunotherapy

For the academic journal, see Immunotherapy (journal).
Immunotherapy
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.
  1. T-cells (represented by objects labeled as 't') are removed from the patient's blood.
  2. Then in a lab setting the gene that encodes for the specific antigen receptors are incorporated into the T-cells.
  3. Thus producing the CAR receptors (labeled as c) on the surface of the cells.
  4. The newly modified T-cells are then further harvested and grown in the lab.
  5. After a certain time period, the engineered T-cells are infused back into the patient.
MeSHD007167
OPS-301 code8-03

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

Activation immunotherapies

Cancer

Main article: Cancer immunotherapy

Cancer treatment used to be focused on killing or removing cancer cells and tumours, with chemotherapy or surgery or radiation. 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[2] and its efficacy is enhanced by 20–30% when cell-based immunotherapy is combined with conventional treatment methods.[2]

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.[33][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] As of 2012, 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

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.[47][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[when?] 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[65][69][70]
Modality Details
Non-antigen specific Monoclonal Antibodies

Depleting:

Non-depleting:

Haematopoietic stem cell transplantation Non-myeloablative Myeloablative
Mesenchymal stem cell transplantation
Regulatory T cell therapy Non-antigen specific Antigen-specific
Low dose IL-2 to expand regulatory T cells
Microbiome manipulation
Antigen specific Peptide therapy Subcutaneous, intradermal, transmucosal (oral, inhaled)

Tolerogenic dendritic cells, liposomes and nanoparticles

Altered peptide ligands

Allergen immunotherapy

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.[citation needed]

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.[71]

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

References

  1. ^ "Immunotherapy | Memorial Sloan Kettering Cancer Center". mskcc.org. Archived from the original on 2019-10-19. Retrieved 2017-07-27.
  2. ^ a b c Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID 29208439.
  3. ^ Conforti L (February 2012). "The ion channel network in T lymphocytes, a target for immunotherapy". Clinical Immunology. 142 (2): 105–106. doi:10.1016/j.clim.2011.11.009. PMID 22189042.
  4. ^ Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA (August 2019). "Current Diagnosis and Management of Small-Cell Lung Cancer". Mayo Clinic Proceedings. 94 (8): 1599–1622. doi:10.1016/j.mayocp.2019.01.034. PMID 31378235.
  5. ^ Riley RS, June CH, Langer R, Mitchell MJ (March 2019). "Delivery technologies for cancer immunotherapy". Nature Reviews. Drug Discovery. 18 (3): 175–196. doi:10.1038/s41573-018-0006-z. PMC 6410566. PMID 30622344.
  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. doi:10.1016/j.hest.2023.02.003. ISSN 2589-238X.
  7. ^ a b Geers D, Shamier MC, Bogers S, den Hartog G, Gommers L, Nieuwkoop NN, et al. (May 2021). "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. doi:10.1126/sciimmunol.abj1750. PMC 9268159. PMID 34035118.
  8. ^ Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN (September 2020). "Pharmaco-Immunomodulatory Therapy in COVID-19". Drugs. 80 (13): 1267–1292. doi:10.1007/s40265-020-01367-z. PMC 7372203. PMID 32696108.
  9. ^ "Immunomodulators and Their Side Effects". www.cancer.org. Archived from the original on 2023-04-08. Retrieved 2021-06-06.
  10. ^ Martino A, Casetti R, Poccia F (January 2007). "Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs". Vaccine. 25 (6): 1023–1029. doi:10.1016/j.vaccine.2006.09.070. PMID 17118497.
  11. ^ Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, et al. (October 2020). "COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses". Nature. 586 (7830): 594–599. Bibcode:2020Natur.586..594S. doi:10.1038/s41586-020-2814-7. PMID 32998157.
  12. ^ Woldemeskel BA, Garliss CC, Blankson JN (May 2021). "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). doi:10.1172/JCI149335. PMC 8121504. PMID 33822770.
  13. ^ Fuge O, Vasdev N, Allchorne P, Green JS (2015). "Immunotherapy for bladder cancer". Research and Reports in Urology. 7: 65–79. doi:10.2147/RRU.S63447. PMC 4427258. PMID 26000263.
  14. ^ Pettenati C, Ingersoll MA (October 2018). "Mechanisms of BCG immunotherapy and its outlook for bladder cancer". Nature Reviews. Urology. 15 (10): 615–625. doi:10.1038/s41585-018-0055-4. PMID 29991725. S2CID 49670901.
  15. ^ Salles G, Barrett M, Foà R, Maurer J, O'Brien S, Valente N, et al. (October 2017). "Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience". Advances in Therapy. 34 (10): 2232–2273. doi:10.1007/s12325-017-0612-x. PMC 5656728. PMID 28983798.
  16. ^ Hoos A (April 2016). "Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations". Nature Reviews. Drug Discovery. 15 (4): 235–247. doi:10.1038/nrd.2015.35. PMID 26965203. S2CID 54550859.
  17. ^ Pento JT (November 2017). "Monoclonal Antibodies for the Treatment of Cancer". Anticancer Research. 37 (11): 5935–5939. doi:10.21873/anticanres.12040. PMC 3288558. PMID 29061772.
  18. ^ Simpson RJ, Bigley AB, Agha N, Hanley PJ, Bollard CM (July 2017). "Mobilizing Immune Cells With Exercise for Cancer Immunotherapy". Exercise and Sport Sciences Reviews. 45 (3): 163–172. doi:10.1249/JES.0000000000000114. PMC 6814300. PMID 28418996.
  19. ^ van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, et al. (April 2008). "Treatment of vulvar intraepithelial neoplasia with topical imiquimod". The New England Journal of Medicine. 358 (14): 1465–1473. doi:10.1056/NEJMoa072685. PMID 18385498.
  20. ^ Buck HW, Guth KJ (October 2003). "Treatment of vaginal intraepithelial neoplasia (primarily low grade) with imiquimod 5% cream". Journal of Lower Genital Tract Disease. 7 (4): 290–293. doi:10.1097/00128360-200310000-00011. PMID 17051086. S2CID 44649376.
  21. ^ Järvinen R, Kaasinen E, Sankila A, Rintala E (August 2009). "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. doi:10.1016/j.eururo.2009.04.009. PMID 19395154.
  22. ^ Davidson HC, Leibowitz MS, Lopez-Albaitero A, Ferris RL (September 2009). "Immunotherapy for head and neck cancer". Oral Oncology. 45 (9): 747–751. doi:10.1016/j.oraloncology.2009.02.009. PMC 8978306. PMID 19442565.
  23. ^ Dani T, Knobler R (January 2009). "Extracorporeal photoimmunotherapy-photopheresis". Frontiers in Bioscience. 14 (14): 4769–4777. doi:10.2741/3566. PMID 19273388.
  24. ^ Eggermont AM, Schadendorf D (June 2009). "Melanoma and immunotherapy". Hematology/Oncology Clinics of North America. 23 (3): 547–64, ix–x. doi:10.1016/j.hoc.2009.03.009. PMID 19464602.
  25. ^ Chuang CM, Monie A, Wu A, Hung CF (May 2009). "Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects". Journal of Biomedical Science. 16 (1): 49. doi:10.1186/1423-0127-16-49. PMC 2705346. PMID 19473507.
  26. ^ Pawlita M, Gissmann L (April 2009). "[Recurrent respiratory papillomatosis: indication for HPV vaccination?]". Deutsche Medizinische Wochenschrift (in German). 134 (Suppl 2): S100–S102. doi:10.1055/s-0029-1220219. PMID 19353471. S2CID 206295083.
  27. ^ Kang N, Zhou J, Zhang T, Wang L, Lu F, Cui Y, et al. (August 2009). "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. doi:10.4161/cbt.8.16.8950. PMID 19471115. S2CID 23222462.
  28. ^ Cheever MA, Higano CS (June 2011). "PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine". Clinical Cancer Research. 17 (11): 3520–3526. doi:10.1158/1078-0432.CCR-10-3126. PMID 21471425. S2CID 135120.
  29. ^ Di Lorenzo G, Buonerba C, Kantoff PW (May 2011). "Immunotherapy for the treatment of prostate cancer". Nature Reviews. Clinical Oncology. 8 (9): 551–561. doi:10.1038/nrclinonc.2011.72. PMID 21606971. S2CID 5337484.
  30. ^ "Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon". Drugs in R&D. 7 (3): 197–201. 2006. doi:10.2165/00126839-200607030-00006. PMID 16752945. S2CID 6427074.
  31. ^ Andersson H, Nyesiga B, Hermodsson T, Enell Smith K, Hägerbrand K, Lindstedt M, et al. (May 2024). "Next-generation CD40 agonists for cancer immunotherapy". Expert Opinion on Biological Therapy. 24 (5): 351–363. doi:10.1080/14712598.2024.2357714. PMID 38764393.
  32. ^ Sabado RL, Balan S, Bhardwaj N (January 2017). "Dendritic cell-based immunotherapy". Cell Research. 27 (1): 74–95. doi:10.1038/cr.2016.157. PMC 5223236. PMID 28025976.
  33. ^ a b c Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (April 2008). "Adoptive cell transfer: a clinical path to effective cancer immunotherapy". Nature Reviews. Cancer. 8 (4): 299–308. doi:10.1038/nrc2355. PMC 2553205. PMID 18354418.
  34. ^ Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. (October 2006). "Cancer regression in patients after transfer of genetically engineered lymphocytes". Science. 314 (5796): 126–129. Bibcode:2006Sci...314..126M. doi:10.1126/science.1129003. PMC 2267026. PMID 16946036.
  35. ^ Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, et al. (June 2008). "Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1". The New England Journal of Medicine. 358 (25): 2698–2703. doi:10.1056/NEJMoa0800251. PMC 3277288. PMID 18565862.
  36. ^ "2008 Symposium Program & Speakers". Cancer Research Institute. Archived from the original on 2008-10-15.
  37. ^ Highfield R (18 June 2008). "Cancer patient recovers after injection of immune cells". The Telegraph. Archived from the original on 12 September 2008. Retrieved 22 December 2019.
  38. ^ "Updated: Novartis buys Dendreon New Jersey plant". Fierce Pharma. 20 December 2012. Archived from the original on 2023-06-07. Retrieved 2021-12-09.
  39. ^ Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, et al. (March 2005). "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. doi:10.4049/jimmunol.174.5.2591. PMC 1403291. PMID 15728465.
  40. ^ Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, et al. (October 2005). "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. doi:10.1084/jem.20050732. PMC 1397916. PMID 16203864.
  41. ^ Dummer W, Niethammer AG, Baccala R, Lawson BR, Wagner N, Reisfeld RA, et al. (July 2002). "T cell homeostatic proliferation elicits effective antitumor autoimmunity". The Journal of Clinical Investigation. 110 (2): 185–192. doi:10.1172/JCI15175. PMC 151053. PMID 12122110.
  42. ^ Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. (November 2008). "Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens". Journal of Clinical Oncology. 26 (32): 5233–5239. doi:10.1200/JCO.2008.16.5449. PMC 2652090. PMID 18809613.
  43. ^ Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, et al. (October 2002). "Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes". Science. 298 (5594): 850–854. Bibcode:2002Sci...298..850D. doi:10.1126/science.1076514. PMC 1764179. PMID 12242449.
  44. ^ Pilon-Thomas S, Kuhn L, Ellwanger S, Janssen W, Royster E, Marzban S, et al. (October 2012). "Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma". Journal of Immunotherapy. 35 (8): 615–620. doi:10.1097/CJI.0b013e31826e8f5f. PMC 4467830. PMID 22996367.
  45. ^ Andersen R, Borch TH, Draghi A, Gokuldass A, Rana MA, Pedersen M, et al. (July 2018). "T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression". Annals of Oncology. 29 (7): 1575–1581. doi:10.1093/annonc/mdy139. PMID 29688262.
  46. ^ Seidel JA, Otsuka A, Kabashima K (2018-03-28). "Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations". Frontiers in Oncology. 8: 86. doi:10.3389/fonc.2018.00086. PMC 5883082. PMID 29644214.
  47. ^ a b Haanen JB, Robert C (2015). "Immune Checkpoint Inhibitors". Progress in Tumor Research. 42: 55–66. doi:10.1159/000437178. ISBN 978-3-318-05589-4. PMID 26382943.
  48. ^ "Immune Checkpoint Inhibitors - National Cancer Institute". National Cancer Institute. 2019-09-24. Archived from the original on 2023-10-22. Retrieved 2020-08-24.
  49. ^ "Immunotherapy By Cancer Type". Cancer Research Institute.
  50. ^ Queirolo P, Boutros A, Tanda E, Spagnolo F, Quaglino P (December 2019). "Immune-checkpoint inhibitors for the treatment of metastatic melanoma: a model of cancer immunotherapy". Seminars in Cancer Biology. 59: 290–297. doi:10.1016/j.semcancer.2019.08.001. hdl:2318/1717353. PMID 31430555.
  51. ^ Moyers JT, Glitza Oliva IC (2021). "Immunotherapy for Melanoma". Immunotherapy. Advances in Experimental Medicine and Biology. Vol. 1342. pp. 81–111. doi:10.1007/978-3-030-79308-1_3. ISBN 978-3-030-79307-4. PMID 34972963.
  52. ^ Cai L, Li Y, Tan J, Xu L, Li Y (September 2023). "Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy". Journal of Hematology & Oncology. 16 (1): 101. doi:10.1186/s13045-023-01499-1. PMC 10478462. PMID 37670328.
  53. ^ Manjunath SR, Ramanan G, Dedeepiya VD, Terunuma H, Deng X, Baskar S, et al. (January 2012). "Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: a case report". Case Reports in Oncology. 5 (1): 114–118. doi:10.1159/000337319. PMC 3364094. PMID 22666198.
  54. ^ Li Y, Zhang T, Ho C, Orange JS, Douglas SD, Ho WZ (December 2004). "Natural killer cells inhibit hepatitis C virus expression". Journal of Leukocyte Biology. 76 (6): 1171–1179. doi:10.1189/jlb.0604372. PMID 15339939.
  55. ^ Doskali M, Tanaka Y, Ohira M, Ishiyama K, Tashiro H, Chayama K, et al. (March 2011). "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. doi:10.1097/CJI.0b013e3182048c4e. PMID 21304407. S2CID 26385818.
  56. ^ Terunuma H, Deng X, Dewan Z, Fujimoto S, Yamamoto N (2008). "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. doi:10.1080/08830180801911743. PMID 18437601. S2CID 27557213.
  57. ^ See DM, Tilles JG (1996). "alpha-Interferon treatment of patients with chronic fatigue syndrome". Immunological Investigations. 25 (1–2): 153–164. doi:10.3109/08820139609059298. PMID 8675231.
  58. ^ Ojo-Amaize EA, Conley EJ, Peter JB (January 1994). "Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome". Clinical Infectious Diseases. 18 (Suppl 1): S157–S159. doi:10.1093/clinids/18.Supplement_1.S157. PMID 8148445.
  59. ^ Kida K, Isozumi R, Ito M (December 2000). "Killing of human Herpes virus 6-infected cells by lymphocytes cultured with interleukin-2 or -12". Pediatrics International. 42 (6): 631–636. doi:10.1046/j.1442-200x.2000.01315.x. PMID 11192519. S2CID 11297558.
  60. ^ "Lymphocyte Proliferation - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-05-10.
  61. ^ "Lymphocyte Proliferation - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-05-10.
  62. ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2007-12-31). Molecular Biology of the Cell. doi:10.1201/9780203833445. ISBN 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. doi:10.17925/eor.2010.04.01.70. ISSN 1756-1795.
  64. ^ Georgievski A, Bellaye PS, Tournier B, Choubley H, Pais de Barros JP, Herbst M, et al. (May 2024). "Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers". Cell Death Dis. 15 (15(5):328): 328. doi:10.1038/s41419-024-06715-5. PMC 11088660. PMID 38734740.
  65. ^ a b Rayner F, Isaacs JD (December 2018). "Therapeutic tolerance in autoimmune disease". Seminars in Arthritis and Rheumatism. 48 (3): 558–562. doi:10.1016/j.semarthrit.2018.09.008. PMID 30348449. S2CID 53034800.
  66. ^ Rotrosen D, Matthews JB, Bluestone JA (July 2002). "The immune tolerance network: a new paradigm for developing tolerance-inducing therapies". The Journal of Allergy and Clinical Immunology. 110 (1): 17–23. doi:10.1067/mai.2002.124258. PMID 12110811. S2CID 30884739.
  67. ^ Stolp J, Zaitsu M, Wood KJ (2019). "Immune Tolerance and Rejection in Organ Transplantation". Immunological Tolerance. Methods in Molecular Biology. Vol. 1899. pp. 159–180. doi:10.1007/978-1-4939-8938-6_12. ISBN 978-1-4939-8936-2. PMID 30649772. S2CID 58542057.
  68. ^ McMurchy AN, Bushell A, Levings MK, Wood KJ (August 2011). "Moving to tolerance: clinical application of T regulatory cells". Seminars in Immunology. Advances in Transplantation. 23 (4): 304–313. doi:10.1016/j.smim.2011.04.001. PMC 3836227. PMID 21620722.
  69. ^ Baker KF, Isaacs JD (March 2014). "Prospects for therapeutic tolerance in humans". Current Opinion in Rheumatology. 26 (2): 219–227. doi:10.1097/BOR.0000000000000029. PMC 4640179. PMID 24378931.
  70. ^ Cooles FA, Isaacs JD (August 2010). "Treating to re-establish tolerance in inflammatory arthritis - lessons from other diseases". Best Practice & Research. Clinical Rheumatology. Pharmacotherapy: Concepts of Pathogenesis and Emerging Treatments. 24 (4): 497–511. doi:10.1016/j.berh.2010.01.007. PMID 20732648.
  71. ^ a b Persaud Y, Memon RJ, Savliwala MN (2024). "Allergy Immunotherapy". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30570988. Retrieved 2024-05-10.
  72. ^ Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, et al. (August 1999). "Long-term clinical efficacy of grass-pollen immunotherapy". The New England Journal of Medicine. 341 (7): 468–475. doi:10.1056/NEJM199908123410702. PMID 10441602. S2CID 14629112.
  73. ^ James C, Bernstein DI (February 2017). "Allergen immunotherapy: an updated review of safety". Current Opinion in Allergy & Clinical Immunology. 17 (1): 55–59. doi:10.1097/ACI.0000000000000335. ISSN 1528-4050. PMC 5644500. PMID 27906697.
  74. ^ MacGinnitie AJ, Rachid R, Gragg H, Little SV, Lakin P, Cianferoni A, et al. (March 2017). "Omalizumab facilitates rapid oral desensitization for peanut allergy". The Journal of Allergy and Clinical Immunology. 139 (3): 873–881.e8. doi:10.1016/j.jaci.2016.08.010. PMC 5369605. PMID 27609658. S2CID 3626708.
  75. ^ "Oral immunotherapy for peanut allergy in young children". National Institutes of Health (NIH). 2022-02-07. Archived from the original on 2023-07-12. Retrieved 2022-06-06.
  76. ^ Loukas A, Prociv P (October 2001). "Immune responses in hookworm infections". Clinical Microbiology Reviews. 14 (4): 689–703, table of contents. doi:10.1128/CMR.14.4.689-703.2001. PMC 89000. PMID 11585781.
  77. ^ Correale J, Farez M (February 2007). "Association between parasite infection and immune responses in multiple sclerosis". Annals of Neurology. 61 (2): 97–108. doi:10.1002/ana.21067. PMID 17230481. S2CID 1033417.
  78. ^ Croese J, O'neil J, Masson J, Cooke S, Melrose W, Pritchard D, et al. (January 2006). "A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors". Gut. 55 (1): 136–137. doi:10.1136/gut.2005.079129. PMC 1856386. PMID 16344586.
  79. ^ Reddy A, Fried B (January 2009). "An update on the use of helminths to treat Crohn's and other autoimmunune diseases". Parasitology Research. 104 (2): 217–221. doi:10.1007/s00436-008-1297-5. PMID 19050918. S2CID 19279688.
  80. ^ Laclotte C, Oussalah A, Rey P, Bensenane M, Pluvinage N, Chevaux JB, et al. (December 2008). "[Helminths and inflammatory bowel diseases]". Gastroenterologie Clinique et Biologique (in French). 32 (12): 1064–1074. doi:10.1016/j.gcb.2008.04.030. PMID 18619749.
  81. ^ Zaccone P, Fehervari Z, Phillips JM, Dunne DW, Cooke A (October 2006). "Parasitic worms and inflammatory diseases". Parasite Immunology. 28 (10): 515–523. doi:10.1111/j.1365-3024.2006.00879.x. PMC 1618732. PMID 16965287.
  82. ^ Donkers SJ, Kirkland MC, Charabati M, Osborne LC (2020). "Perspectives of People with Multiple Sclerosis About Helminth Immunotherapy". International Journal of MS Care. 22 (1): 43–51. doi:10.7224/1537-2073.2019-044. PMC 7041615. PMID 32123528.
  83. ^ a b Brooker S, Bethony J, Hotez PJ (2004). "Human hookworm infection in the 21st century". Advances in Parasitology. 58: 197–288. doi:10.1016/S0065-308X(04)58004-1. ISBN 9780120317585. PMC 2268732. PMID 15603764.
  84. ^ Fujiwara RT, Cançado GG, Freitas PA, Santiago HC, Massara CL, Dos Santos Carvalho O, et al. (2009). "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. doi:10.1371/journal.pntd.0000399. PMC 2654967. PMID 19308259.
  85. ^ Carvalho L, Sun J, Kane C, Marshall F, Krawczyk C, Pearce EJ (January 2009). "Review series on helminths, immune modulation and the hygiene hypothesis: mechanisms underlying helminth modulation of dendritic cell function". Immunology. 126 (1): 28–34. doi:10.1111/j.1365-2567.2008.03008.x. PMC 2632707. PMID 19120496.
  86. ^ Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, et al. (June 2009). "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. doi:10.1084/jem.20082779. PMC 2715056. PMID 19468064.
  87. ^ Reynolds LA, Finlay BB, Maizels RM (November 2015). "Cohabitation in the Intestine: Interactions among Helminth Parasites, Bacterial Microbiota, and Host Immunity". Journal of Immunology. 195 (9): 4059–4066. doi:10.4049/jimmunol.1501432. PMC 4617609. PMID 26477048.
  88. ^ Loke P, Lim YA (June 2015). "Helminths and the microbiota: parts of the hygiene hypothesis". Parasite Immunology. 37 (6): 314–23. doi:10.1111/pim.12193. PMC 4428757. PMID 25869420.
  89. ^ Hong CH, Tang MR, Hsu SH, Yang CH, Tseng CS, Ko YC, et al. (September 2019). "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. Bibcode:2019JPPB..19811560H. doi:10.1016/j.jphotobiol.2019.111560. PMID 31336216. S2CID 198191485.
  90. ^ Chang HY, Li MH, Huang TC, Hsu CL, Tsai SR, Lee SC, et al. (February 2015). "Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells". Journal of Proteome Research. 14 (2): 1250–1262. doi:10.1021/pr5011873. PMID 25556991.
  91. ^ Nagaya T, Okuyama S, Ogata F, Maruoka Y, Choyke PL, Kobayashi H (May 2019). "Near infrared photoimmunotherapy using a fiber optic diffuser for treating peritoneal gastric cancer dissemination". Gastric Cancer. 22 (3): 463–472. doi:10.1007/s10120-018-0871-5. PMC 7400986. PMID 30171392.
  92. ^ Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H (November 2011). "Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules". Nature Medicine. 17 (12): 1685–1691. doi:10.1038/nm.2554. PMC 3233641. PMID 22057348.
  93. ^ Sato K, Sato N, Xu B, Nakamura Y, Nagaya T, Choyke PL, et al. (August 2016). "Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy". Science Translational Medicine. 8 (352): 352ra110. doi:10.1126/scitranslmed.aaf6843. PMC 7780242. PMID 27535621.
  94. ^ Nagaya T, Nakamura Y, Sato K, Harada T, Choyke PL, Kobayashi H (June 2016). "Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT)". Journal of Controlled Release. 232: 1–8. doi:10.1016/j.jconrel.2016.04.003. PMC 4893891. PMID 27059723.
  95. ^ Zhen Z, Tang W, Wang M, Zhou S, Wang H, Wu Z, et al. (February 2017). "Protein Nanocage Mediated Fibroblast-Activation Protein Targeted Photoimmunotherapy To Enhance Cytotoxic T Cell Infiltration and Tumor Control". Nano Letters. 17 (2): 862–869. Bibcode:2017NanoL..17..862Z. doi:10.1021/acs.nanolett.6b04150. PMID 28027646.
Quelle: http://en.wikipedia.org/wiki/Immunomodulatory