Immuno - oncology is a branch of medicine that studies the functions of the immune system in oncological diseases. The therapeutic direction in the framework of immuno-oncology is the immunotherapy of tumors. Tumor immunotherapy is usually divided into active, passive or hybrid. Immunotherapy is based on the fact that cancer cells have molecules on their surface that can be recognized by immune system receptors (antibodies and / or cell receptors).
Active immunotherapy involves the use of the body's own immune cells to fight cancer cells. Passive immunotherapy involves the administration of antibodies, lymphocytes and cytokines.
Antibodies are molecules of the immune system that can recognize antigens on the surface of cells. Antibodies capable of binding to cancer antigens are used to treat cancer. Typical targets for passive cancer immunotherapy are CD20 , CD274, and CD279 molecules . When bound to a cancer antigen, antibodies cause cancer cell death by inducing antibody-dependent cell cytotoxicity and activation of the complement system. In addition, by blocking the receptors of cancer cells, antibodies prevent their interaction with the corresponding ligands, which also leads to cell death. Examples of such antibodies are alemtuzumab , rituximab .
Active immunotherapy uses the capabilities of immune cells to destroy target cells. One approach is the isolation of immune cells from blood or from tumor tissue. Tumor-specific cells are then cultured and introduced back into the patient, after which they attack the tumor. The cells that can be used in such therapy are natural killer cells, cytotoxic T-lymphocytes and dendritic cells. Another way is to influence the immune cells in the body. For this purpose, antibodies to CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) are used, as a result of which lymphocytes are activated and begin to destroy tumor cells.
Interleukin-2 and interferon -α are cytokines that can improve the antitumor immune response. Interferon-α is used in the treatment of hairy cell leukemia, Kaposi’s sarcoma, follicular lymphoma, chronic myeloid leukemia and melanoma. Interleukin-2 is used to treat melanoma and renal cell carcinoma.
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History
Immunotherapy for the treatment of cancer became possible after the introduction of monoclonal antibody production technology in 1975.
Cellular immunotherapy was introduced into practice in the late 1980s. [one]
In 1987, the CTLA-4 molecule was discovered, which prevents the attack of T-lymphocytes on tumor cells. In a mouse model in 1996, it was shown that blocking CTLA-4 antibodies allows immune cells to destroy the tumor. [2] In 1999, the biotechnology company Medarex acquired the rights to produce this antibody. In 2010, after the purchase of Medarex, Bristol-Myers Squibb announced an average life extension of 10 months for patients with metastatic melanoma when using an antibody. [2]
In the early 1990s, a PD-1 molecule was discovered in dying T-lymphocytes ("Programmed death 1" - "programmed death 1 molecule"). Antibodies directed to PD-1 are able to stop the death of T-lymphocytes, which can attack the tumor. The effectiveness of treatment with such antibodies was shown in 2008. In 2013, it was reported that such therapy was effective in treating melanoma, kidney cancer, and lung cancer. [2]
In 1997, the use of the rituximab antibody for the treatment of follicular lymphoma was first approved. After that, more than 10 drugs were approved for cancer treatment, including alemtuzumab (2001), ofatumumab (2009), ipilimumab (2011) and other antibodies.
In 2003, a method for treating cancer with cytokines was introduced. [3] Side effects arising from the intravenous administration of cytokines [4] made attempts to isolate cells from the human body, process them with cytokines and reverse administration [5] .
Cellular immunotherapy with the anti-cancer vaccine sipuleycel-T was approved for the treatment of prostate cancer in 2010. [6] [7]
Also in 2010, a successful attempt was made to treat cancer with T-lymphocytes with a chimeric receptor for cancer antigen ( CAR- therapy). This treatment method is an example of personalized treatment based on the genetic modification of a patient's T lymphocytes. [2]
In mid-2016, the use of the PD-L1 inhibitor, atesolizumab, and two PD-1 inhibitors, nivolumab and pembrolizumab, was approved.
Cellular Immunotherapy
Dendritic Cell Therapy
Dendritic cell immunotherapy improves the antitumor immune response. In this type of therapy, dendritic cells are incubated with a cancer antigen, after which activated mature dendritic cells are returned to the patient's body, where they in turn activate T-lymphocytes that can destroy the tumor. [8] .
Another promising way is vaccination by introducing lysates of tumor tissue. [9]
Dendritic cells can also be activated in vivo by causing tumor cells to express GM-CSF. This can be achieved by genetic modification of tumor cells. Another way to activate dendritic cells is to use antibodies to receptors on their surface. Toll-like receptors TLR3, TLR7, TLR8 and the CD40s molecule can be used as targets. [eight]
Conjugated Antibody Therapy
Two types of antibodies can be used in antibody treatment:
- conventional monoclonal antibodies without additional molecules;
- conjugated monoclonal antibodies that bind a molecule that is cytotoxic or radioactive. In this case, the antibody is able to bind to the tumor cell, and the toxic component ensures the death of the target cell.
See also
- Cancer Immunotherapy
Notes
- ↑ Rosenberg SA Adoptive immunotherapy of cancer: accomplishments and prospects (English) // Cancer Treat Rep : journal. - 1984. - January ( vol. 68 , no. 1 ). - P. 233–55 . - PMID 6362866 .
- ↑ 1 2 3 4 Couzin-Frankel, J. Cancer Immunotherapy (Eng.) // Science. - 2013 .-- 20 December ( vol. 342 , no. 6165 ). - P. 1432-1433 . - DOI : 10.1126 / science.342.6165.1432 .
- ↑ Yang Q., Hokland ME, Bryant JL, Zhang Y., Nannmark U., Watkins SC, Goldfarb RH, Herberman RB, Basse PH Tumor-localization by adoptively transferred, interleukin-2-activated NK cells leads to destruction of well- established lung metastases (English) // Int. J. Cancer : journal. - 2003 .-- July ( vol. 105 , no. 4 ). - P. 512-9 . - DOI : 10.1002 / ijc.11119 . - PMID 12712443 .
- ↑ Egawa K. Immuno-cell therapy of cancer in Japan (Eng.) // Anticancer Res. : journal. - 2004. - Vol. 24 , no. 5C . - P. 3321-6 . - PMID 15515427 .
- ↑ Li K., Li CK, Chuen CK, Tsang KS, Fok TF, James AE, Lee SM, Shing MM, Chik KW, Yuen PM Preclinical ex vivo expansion of G-CSF-mobilized peripheral blood stem cells: effects of serum- free media, cytokine combinations and chemotherapy (English) // Eur. J. Haematol. : journal. - 2005 .-- February ( vol. 74 , no. 2 ). - P. 128-35 . - DOI : 10.1111 / j.1600-0609.2004.00343.x . - PMID 15654904 .
- ↑ Strebhardt K., Ullrich A. Paul Ehrlich's magic bullet concept: 100 years of progress (Eng.) // Nature Reviews. Cancer : journal. - 2008 .-- June ( vol. 8 , no. 6 ). - P. 473-80 . - DOI : 10.1038 / nrc2394 . - PMID 18469827 .
- ↑ Waldmann TA Immunotherapy: past, present and future (Eng.) // Nature Medicine : journal. - 2003 .-- March ( vol. 9 , no. 3 ). - P. 269-77 . - DOI : 10.1038 / nm0303-269 . - PMID 12612576 .
- ↑ 1 2 Palucka K., Banchereau J. Dendritic-cell-based therapeutic cancer vaccines (English) // Immunity. - Cell Press 2013 .-- July ( vol. 39 , no. 1 ). - P. 38-48 . - DOI : 10.1016 / j.immuni.2013.07.004 . - PMID 23890062 .
- ↑ Hirayama M., Nishimura Y. The present status and future prospects of peptide-based cancer vaccines (English) // International Immunology : journal. - 2016. - DOI : 10.1093 / intimm / dxw027 . - PMID 27235694 .
Links
- Cancer Research Institute - What is Cancer Immunotherapy
- Association for Immunotherapy of Cancer
- Society for Immunotherapy of Cancer
- And Then There Were Five , Economist .
- Discover the Science of Immuno-Oncology (Link not available) . Bristol-Myers Squibb . Date of treatment March 13, 2014. Archived October 10, 2014.
- Eggermont A., Finn O. Advances in immuno-oncology (neopr.) . - Oxford University Press.
- Immuno-Oncology: Investigating Cancer Therapies Powered by the Immune System . Merck Serono . Date of treatment March 13, 2014.