ROLE OF MONOCLONAL ANTIBODIES AGAINST THE PROGRAMMABLE DEATH (PD-1) RECEPTOR OF T-CELLS IN TARGETED THERAPY OF MELANOMA
Main Article Content
Authors
K.N. Mukantayev
National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan
K.K. Mukanov
National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan
A. Zhylkibayev
National Center for Biotechnology, 13/5, Korgalzhyn road, Astana, 010000, Kazakhstan
Abstract
Oncogenic cells have intrinsic properties for evading attack by the immune system, which largely contribute to the oncogenic pathology. Therefore, the development of drugs that can block these properties represents an important goal toward obtaining effective strategies to cure cancer. Currently, monoclonal antibodies targeting the programmable cell death 1 (PD-1) receptor and its ligand (PD-L1) are widely used in targeted therapy, which show high effectivity in clinical studies resulting in a significant increase in the duration of anticancer immunity.
The PD-1/PD-L1 signaling pathway was recently identified as a mechanism of the negative regulation of the immune system, and as the main mechanism by which oncogenic cells evade the body’s immune system. Moreover, the expression of PD-1 receptor in the tumour microenvironment cells is related to several other signaling pathways involving both hematopoietic and non-hematopoietic cells. The interaction of PD-1 and PD-L1 inhibits the activity of cytotoxic T-cells and tumour-infiltrating lymphocytes with increased T-cell suppressor activity. Consequently, the PD-1/PD-L1 signaling pathway promotes tumour cells to evade the immune response. Therefore, blockage of PD-1/PD-L1 enhances antitumor immunity, reduces the number of T-cell suppressors and suppresses their activity, and restores the activity of cytotoxic T-cells.
The PD1 receptor and it is ligands PD-L1 and PD-L2 are representatives of the immunoglobulin superfamily and are part of the "immunological control points" system, the main functions of which include the regulation and modulation of the immune response, reduction of immune cell-induced damage in organs and tissues, and prevention of autoimmune processes.
Accordingly, development of therapeutic anti-PD1 and anti-PD-L1 monoclonal antibodies that could lead to the reactivation of a specific antitumor immune response is a promising strategy of tumour immunotherapy. To date, monoclonal antibodies blocking PD-1/PD-L1 have achieved good results and were approved by the Food and Drug Administration.
Keywords
monoclonal antibodies, melanoma, PD1, PD-L1, receptor, immunotherapy of tumours
Article Details
References
Buzdin A.A., Zhavoronkov A.A., Borisov N.M. Personalizirovannyye podkhod i sistema prinyatiya klinicheskogo resheniya v onkologii na osnovanii analiza aktivatsii signal'nykh putey/ The personalized approach and the system of clinical decision making in oncology based on the analysis of the activation of signaling pathways. Almanah. Innovacii v onkologii / Almanac. Innovations in oncology, 2015, pp. 18-24. www.eafo.info | www.sk.ru.
Subburayalu J., Wilde B. “Programmed-cell-death”- Protein 1 (PD-1/CD279). Nephrologe, 2016, vol. 11, pp. 70-72. doi: 10.1007/s11560-015-0037-y.
URL.
URL.
URL.
URL.
Riemer A.B., Hantusch B., Sponer B., Kraml G., Hafner C., Zielinski C.C., Scheiner O., Pehamberger H., Jensen-Jarolim E. High-molecular-weight melanoma-associated antigen mimotope immunizations induce antibodies recognizing melanoma cells. Cancer Immunology Immunotherapy, 2005, vol. 54, pp. 677-684. doi: 10.1007/s00262-004-0632-7.
Hamanishi J., Mandai M., Matsumura N., Abiko K., Baba T., Konishi I. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. International Journal of Clinical Oncology, 2016, vol. 21. pp. 462-473. doi: 10.1007/s10147-016-0959-z.
Wang J., Yuan R., Song W., Sun J., Liu D., Li Z. PD-1, PD-L1 (B7-H1) and Tumor-Site Immune Modulation Therapy: The Historical Perspective. Journal of Hematology & Oncology, 2017, vol. 10, pp. 34-42. doi: 10.1186/s13045-017-0403-5.
Wang D., Guo L., Wu X. Checkpoint inhibitors in immunotherapy of ovarian cancer. Tumor Biology, 2015, vol. 36, pp. 33-39. doi: 10.1007/s13277-014-2848-2.
Fujita K., Ikarashi H., Takakuwa K., et al. Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clinical Cancer Research, 1995, vol. 1, pp. 501-507. PMID: 9816009.
Manjunath S.R., Ramanan G., Dedeepiya V.D., et al. Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: A case report. Case Reports in Oncology, 2012, vol. 5, pp. 114-118. doi: 10.1159/000337319.
Spellman A., Tang S.C. Immunotherapy for breast cancer: past, present, and future. Cancer Metastasis Review., 2016, vol. 35, pp. 525-546. doi: 10.1007/s10555-016-9654-9.
Mohit E., Hashemi A., Allahyari M. Breast cancer immunotherapy: monoclonal antibodies and peptide-based vaccines. Expert Review of Clinical Immunology, 2014, vol. 10, pp. 927-961. doi: 10.1586/1744666X.2014.916211.
Barrow C., Browning J., MacGregor D., et al. antigen expression in melanoma varies according to antigen and stage. Clinical Cancer Research, 2006, vol. 12, pp. 764-771. doi: 10.1158/1078-0432.CCR-05-1544.
Mittendorf E.A., Holmes J.P., Ponniah S., Peoples G.E. The E75 HER2/neu peptide vaccine. Cancer Immunol Immunother, 2008, vol. 57, pp. 1511-1521. doi: 10.1007/s00262-008-0540-3.
Peoples G.E., Holmes J.P., Hueman M.T., et al. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clinical Cancer Research, 2008, vol. 14, pp. 797-803. doi: 10.1158/1078-0432.CCR-07-1448.
Niccolai E., Amedei A. Vaccine Immunotherapy Strategies in Colorectal Cancer Treatment. Single Cell Biology, 2012, vol. 1, pp. 1-7. doi: 10.4172/2168-9431.1000102.
Menon A.G., Kuppen P.J., van der Burg S.H., et al. Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients. Cancer Gene Therapy, 2003, vol. 10, pp. 509-517. doi: 10.1038/sj.cgt.7700600.
Kaufman H.L., Lenz H.J., Marshall J., Singh D., et al. Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clinical Cancer Research, 2008, vol. 14, pp. 4843-4849. doi: 10.1158/1078-0432.CCR-08-0276.
Elkord E., Dangoor A., Burt D.J., Southgate T.D., et al. Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4). Cancer Immunology Immunotherapy, 2009, vol. 58, pp. 1657-1667. doi: 10.1007/s00262-009-0674-y.
Giantonio B.J., Catalano P.J., Meropol N.J., O’Dwyer P.J., Mitchell E.P., Alberts S.R. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. Journal of Clinical Oncology, 2007, vol. 25, pp. 1539-1544. doi: 10.1200/JCO.2006.09.6305.
Speetjens F.M., Kuppen P.J., Welters M.J., et al. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clinical Cancer Research, 2009, vol. 15, pp. 1086-1095. doi: 10.1158/1078-0432.CCR-08-2227.
Dalerba P., Ricci A., Russo V., Rigatti D., et al. High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: implications for protocol design of therapeutic antigen-specific vaccination strategies. International Journal Cancer, 1998, vol. 17, no. 77 (2), pp. 200-204. PMID: 9650552.
Thara E., Barzi A. Immunotherapeutic Strategies for Colon Cancer: Monoclonal Antibody Therapy. Current Colorectal Cancer Reports, 2015, vol. 11, pp. 84-91. doi: 10.1007/s11888-015-0260-y.
Mamalis A., Garcha M., Jagdeo J. Targeting the PD-1 pathway: a promising future for the treatment of melanoma. Archives of Dermatological Research, 2014, vol. 306, pp. 511-519. doi: 10.1007/s00403-014-1457-7.
Shimizu T., Seto T., Hirai F., Takenoyama M., et al. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors. Investigational New Drugs., 2016, vol. 34, pp. 347-354. doi: 10.1007/s10637-016-0347-6.
Yamazaki N., Takenouchi T., Fujimoto M., et al. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemotherapy Pharmacology, 2017, vol. 79, pp. 651-660. doi: 10.1007/s00280-016-3237-x.
Francisco L.M., Sage P.T., Sharpe A.H. The PD-1 pathway in tolerance and autoimmunity. Immunology Review, 2010, vol. 236, pp. 219-242. doi: 10.1111/j.1600-065X.2010.00923.x.
Barber D.L., Wherry E.J., Masopust D., Zhu B., et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature, 2006, vol. 439, pp. 682-687. doi: 10.1038/nature04444.
Dong Y., Sun Q., Zhang X. PD-1 and its ligands are important immune checkpoints in cancer. Oncotarget, 2017, vol. 8, no. 2, pp. 2171-2186. doi: 10.18632/oncotarget.13895.
Ishida Y., Agata Y., Shibahara K., Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 1992, vol. 11, pp. 3887-3895. PMID: 1396582.
Shinohara T., Taniwaki M., Ishida Y., Kawaichi M., Honjo T. Structure and chromosomal localization of the human PD-1 gene (PDCD1). Genomics, 1994, vol. 23, pp. 704-706. doi: 10.1006/geno.1994.1562.
Starr R., Willson T.A., Viney E.M., et al. A family of cytokine-inducible inhibitors of signaling. Nature, 1997, vol. 387, pp. 917-921. doi: 10.1038/43206.
Lorenz U. SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunology Review., 2009, vol. 228, no. 1, pp. 342-359. doi: 10.1111/j.1600-065X.2008.00760.x.
Agata Y., Kawasaki A., Nishimura H., Ishida Y., Tsubata T., Yagita H., Honjo T. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. International Immunology, 1996, vol. 8, pp. 765-772.
Matsuzaki J., Gnjatic S., Mhawech-Fauceglia P., Beck A., et al. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proceedings National Academy Sciences USA, 2010, vol. 107, pp. 7875-7880. doi: 10.1073/pnas.1003345107.
Saito H., Kuroda H., Matsunaga T., Osaki T., Ikeguchi M. Increased PD-1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer. Journal of Surgical Oncology, 2013, vol. 107, pp. 517-522. doi: 10.1002/jso.23281.
Kao C., Oestreich K.J., Paley M.A., Crawford A., et al. Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection. Nature Immunology, 2011, vol. 12, pp. 663-671. doi: 10.1038/ni.2046.
Sanmamed M.F., Chen L. Inducible expression of B7-H1 (PD-L1) and its selective role in tumor site immune modulation. Cancer Journal, 2014, vol. 20, pp. 256-261. doi: 10.1097/PPO.0000000000000061.
Mazanet M.M., Hughes C.C.W. B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis. The Journal of Immunology, 2002, vol. 169, pp. 3581-3588. doi: 10.4049/jimmunol.169.7.3581.
Curiel T.J., Wei S., Dong H., Alvarez X., Cheng P., et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nature Medicine, 2003, vol. 9, pp. 562-567. doi: 10.1038/nm863.
Sznol M., Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer-response. Clinical Cancer Research, 2013, vol. 19, pp. 5542. doi: 10.1158/1078-0432.CCR-13-2234.
Hamid O., Robert C., Daud A., Hodi F.S., Hwu W-J., et al. Safety and tumor responses with lambrolizumab (anti–PD-1) in melanoma. The New England Journal of Medicine, 2013, vol. 369, pp. 134-144. doi: 10.1056/NEJMoa1305133.
Taube J.M., Anders R.A., Young G.D., Xu H., et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Science Translational Medicine, 2012, vol. 4, pp. 127-137. doi: 10.1126/scitranslmed.3003689.