Recombinant Human Cyclophilin A in Combination with Adoptive T-cell Therapy Improves the Efficacy of Cancer Immunotherapy in Experimental Models in vivo
Tóm tắt
Adoptive T-cell therapy (ACT) is successfully applied in cancer treatment; however, its efficiency can be limited by a low viability, short persistence time, and loss of functional activity of T-cells after adoptive transfer. The search for novel immunomodulators that can improve the viability, expansion, and functions of T-cells after their infusion with the minimal side effects could contribute to the development of more efficient and safe ACT strategies. Recombinant human cyclophilin A (rhCypA) is of particular interest in this respect, as it exhibits pleiotropic immunomodulatory activity and stimulates both innate and adaptive anti-tumor immunity. Here, we evaluated the effect of rhCypA on the efficacy of ACT in the mouse EL4 lymphoma model. Lymphocytes from transgenic 1D1a mice with an inborn pool of EL4-specific T-cells were used as a source of tumor-specific T-cells for ACT. In models of immunocompetent and immunodeficient transgenic mice, the course (3 days) rhCypA administration was shown to significantly stimulate EL4 rejection and prolong the overall survival of tumor-bearing mice after adoptive transfer of lowered doses of transgenic 1D1a cells. Our studies showed that rhCypA significantly improved the efficacy of ACT by enhancing the effector functions of tumor-specific cytotoxic T-cells. These findings open up the prospects for the development of innovative strategies of adoptive T-cell immunotherapy for cancer using rhCypA as an alternative to existing cytokine therapies.
Tài liệu tham khảo
Met, Ö., Jensen, K., Chamberlain, C., Donia, M., and Svane, I. (2019) Principles of adoptive T cell therapy in cancer, Semin. Immunopathol., 41, 49-58, https://doi.org/10.1007/s00281-018-0703-z.
Zhang, H., and Chen, J. (2018) Current status and future directions of cancer immunotherapy, J. Cancer., 9, 1773-1781, https://doi.org/10.7150/jca.24577.
Zhao, Q., Jiang, Y., Xiang, S., Kaboli, P., Shen, J., Zhao, Y., Wu, X., Du, F., Li, M., Cho, C., Li, J., Wen, Q., Liu, T., Yi, T., and Xiao, Z. (2021) Engineered TCR-T cell immunotherapy in anticancer precision medicine: pros and cons, Front. Immunol., 12, 658753, https://doi.org/10.3389/fimmu.2021.658753.
June, C., O’Connor, R., Kawalekar, O., Ghassemi, S., and Milone, M. (2018) CAR T cell immunotherapy for human cancer, Science, 359, 1361-1365, https://doi.org/10.1126/science.aar6711.
Mescher, M., Popescu, F., Gerner, M., Hammerbeck, C., and Curtsinger, J. (2007) Activation-induced non-responsiveness (anergy) limits CD8 T cell responses to tumors, Semin. Cancer Biol., 17, 299-308, https://doi.org/10.1016/j.semcancer.2007.06.008.
William, Y., Ho, C., and Greenberg, P. (2002) Adoptive therapy with CD8+ T cells: it may get by with a little help from its friends, J. Clin. Invest., 110, 1415-1417, https://doi.org/10.1172/JCI17214.
Srivastava, S., and Riddell, S. (2018) Chimeric antigen receptor T cell therapy: challenges to bench-to-bedside efficacy, J. Immunol., 200, 459-468, https://doi.org/10.4049/jimmunol.1701155.
Yamamoto, T., Lee, P., Vodnala, S., Gurusamy, D., Kishton, R., Yu, Z., Eidizadeh, A., Eil, R., Fioravanti, J., Gattinoni, L., Kochenderfer, J., Fry, T., Aksoy, B., Hammerbacher, J., Cruz, A., Siegel, R., Restifo, N., and Klebanoff, C. (2019) T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy, J. Clin. Invest., 129, 1551-1565, https://doi.org/10.1172/JCI121491.
Chandran, S., Somerville, R., Yang, J., Sherry, R., Klebanoff, C., Goff, S., Wunderlich, J., Danforth, D., Zlott, D., Paria, B., Sabesan, A., Srivastava, A., Xi, L., Pham, T., Raffeld, M., White, D., Toomey, M., Rosenberg, S., and Kammula, U. (2017) Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study, Lancet Oncol., 18, 792-802, https://doi.org/10.1016/S1470-2045(17)30251-6.
Veatch, J., Lee, S., Fitzgibbon, M., Chow, I., Jesernig, B., Schmitt, T., Kong, Y., Kargl, J., Houghton, A., Thompson, J., McIntosh, M., Kwok, W., and Riddell, S. (2018) Tumor-infiltrating BRAFV600E-specific CD4+ T cells correlated with complete clinical response in melanoma, J. Clin. Invest., 128, 1563-1568, https://doi.org/10.1172/JCI98689.
Berraondo, P., Sanmamed, M., Ochoa, M., Etxeberria, I., Aznar, M., Pérez-Gracia, J., Rodríguez-Ruiz, M., Ponz-Sarvise, M., Castañón, E., and Melero, I. (2019) Cytokines in clinical cancer immunotherapy, Br. J. Cancer, 120, 6-15, https://doi.org/10.1038/s41416-018-0328-y.
Choudhry, H., Helmi, N., Abdulaal, W., Zeyadi, M., Zamzami, M., Wu, W., Mahmoud, M., Warsi, M., Rasool, M., and Jamal, M. (2018) Prospects of IL-2 in cancer immunotherapy, Biomed. Res. Int., 2018, 9056173, https://doi.org/10.1155/2018/9056173.
Rosenberg, S., Yang, J., White, D., and Steinberg, S. (1998) Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response, Ann. Surg., 228, 307-319, https://doi.org/10.1097/00000658-199809000-00004.
Nguyen, L., Saibil, S., Sotov, V., Le, M., Khoja, L., Ghazarian, D., Bonilla, L., Majeed, H., Hogg, D., Joshua, A., Crump, M., Franke, N., Spreafico, A., Hansen, A., Al-Habeeb, A., Leong, W., Easson, A., Reedijk, M., Goldstein, D., McCready, D., Yasufuku, K., Waddell, T., Cypel, M., Pierre, A., Zhang, B., Boross-Harmer, S., Cipollone, J., Nelles, M., Scheid, E., Fyrsta, M., Lo, C., Nie, J., Yam, J., Yen, P., Gray, D., Motta, V., Elford, A., DeLuca, S., Wang, L., Effendi, S., Ellenchery, R., Hirano, N., Ohashi, P., and Butler, M. (2019) Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2, Cancer Immunol. Immunother., 68, 773-785, https://doi.org/10.1007/s00262-019-02307-x.
Kalinina, A., Silaeva, Yu., Kazansky, D., and Khromykh, L. (2019) The role of recombinant human Cyclophilin A in the antitumor immune response, Acta Naturae, 11, 63-67, https://doi.org/10.32607/20758251-2019-11-2-63-67.
Nigro, P., Pompilio, G., and Capogrossi, M. (2013) Cyclophilin A: a key player for human disease, Cell Death Dis., 4, e888, https://doi.org/10.1038/cddis.2013.410.
Khromykh, L., Kulikova, N., Anfalova, T., Muranova, T., Abramov, V., Vasiliev, A., Khlebnikov, V., and Kazansky, D. (2007) Cyclophilin A produced by thymocytes regulates the migration of murine bone marrow cells, Cell Immunol., 249, 46-53, https://doi.org/10.1016/j.cellimm.2007.11.002.
Xu, Q., Leiva, M., Fischkoff, S., Handschumacher, R., and Lyttle, C. (1992) Leukocyte chemotactic activity of cyclophilin, J. Biol. Chem., 267, 11968-11971.
Dawar, F., Xiong, Y., Khattak, M., Li, J., Lin, L., Mei, J. (2017) Potential role of cyclophilin A in regulating cytokine secretion, J. Leukoc. Biol., 102, 989-992, https://doi.org/10.1189/jlb.3RU0317-090RR.
Zamkova, M., Kalinina, A., Silaeva, Y., Persiyantseva, N., Bruter, A., Deikin, A., Khromykh, L., and Kazansky, D. (2019) Dominant role of the α-chain in rejection of tumor cells bearing a specific alloantigen in TCRα transgenic mice and in in vitro experiments, Oncotarget, 10, 4808-4821, https://doi.org/10.18632/oncotarget.27093.
Silaeva, Y., Kalinina, A., Vagida, M., Khromykh, L., Deikin, A., Ermolkevich, T., Sadchikova, E., Goldman, I., and Kazansky, D. (2013) Decrease in pool of T lymphocytes with surface phenotypes of effector and central memory cells under influence of TCR transgenic β-chain expression, Biochemistry (Moscow), 78, 549-559, https://doi.org/10.1134/S0006297913050143.
Kalinina, A., Kolesnikov, A., Kozyr, A., Kulikova, N., Zamkova, M., Kazansky, D., and Khromykh, L. (2022) Preparative production and purification of recombinant human Cyclophilin A, Biochemistry (Moscow), 87, 259-268, https://doi.org/10.1134/S0006297922030063.
Khromykh, L. M., Kalinina, A. A., Kozyr, A. V., Kolesnikov, A. V., Silaeva, Yu. Yu., and Kazansky, D. B. Patent No. 2603283. Russian Federation. 2015.
Silaeva, Y., Grinenko, T., Vagida, M., Kalinina, A., Khromykh, L., and Kazansky, D. (2014) Immune selection of tumor cells in TCR β-chain transgenic mice, J . Immunotoxicol., 11, 393-399, https://doi.org/10.3109/1547691X.2013.861548.
Kalinina, A., Zamkova, M., Antoshina, E., Trukhanova, L., Gorkova, T., Kazansky, D., and Khromykh, L. (2019) Analyses of the toxic properties of recombinant human Cyclophilin A in mice, J. Immunotoxicol., 16, 182-190, https://doi.org/10.1080/1547691X.2019.1665597.