Abstract
Since T cells can recognize tumor-associated antigens and eliminate cancer cells, preclinical and clinical developments of therapy have been leveraging on the use of autologous tumor-infiltrating lymphocytes (TILs). Target metastatic tumor is excised from patient by trained surgeon and then transferred to laboratory, where is cut into small fragments. Lymphocytes are then enriched in culture with interleukin 2 and after several days propagated in rapid expansion phase. When TIL product is ready, patient receives lymphodepleting chemotherapy, and then TILs are infused followed by treatment with high-dose interleukin 2. Therapy with TIL has shown to be an effective treatment strategy in melanoma, even after melanoma progression following immune checkpoint inhibitor therapy with remarkable responses and improvement of progression-free survival. Recently, genetically modified TILs have been tested with a goal to further improve clinical activity.
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References
Andersen, R., Donia, M., Ellebaek, E., Borch, T. H., Kongsted, P., Iversen, T. Z., Holmich, L. R., Hendel, H. W., Met, O., Andersen, M. H., Thor Straten, P., & Svane, I. M. (2016). Long-lasting complete responses in patients with metastatic melanoma after adoptive cell therapy with tumor-infiltrating lymphocytes and an attenuated IL2 regimen. Clinical Cancer Research, 22(15), 3734–3745.
Besser, M. J., Shapira-Frommer, R., Treves, A. J., Zippel, D., Itzhaki, O., Hershkovitz, L., Levy, D., Kubi, A., Hovav, E., Chermoshniuk, N., Shalmon, B., Hardan, I., Catane, R., Markel, G., Apter, S., Ben-Nun, A., Kuchuk, I., Shimoni, A., Nagler, A., & Schachter, J. (2010). Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clinical Cancer Research, 16(9), 2646–2655.
Chamberlain, C. A., Bennett, E. P., Kverneland, A. H., Svane, I. M., Donia, M., & Met, O. (2022). Highly efficient PD-1-targeted CRISPR-Cas9 for tumor-infiltrating lymphocyte-based adoptive T cell therapy. Molecular Therapy - Oncolytics, 24, 417–428.
Chesney, J., Lewis, K. D., Kluger, H., Hamid, O., Whitman, E., Thomas, S., Wermke, M., Cusnir, M., Domingo-Musibay, E., Phan, G. Q., Kirkwood, J. M., Hassel, J. C., Orloff, M., Larkin, J., Weber, J., Furness, A. J. S., Khushalani, N. I., Medina, T., Egger, M. E., Graf Finckenstein, F., Jagasia, M., Hari, P., Sulur, G., Shi, W., Wu, X., & Sarnaik, A. (2022). Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: Pooled analysis of consecutive cohorts of the C-144-01 study. Journal for Immunotherapy of Cancer, 10(12).
Chu, Y., Milner, J., Lamb, M., Maryamchik, E., Rigot, O., Ayello, J., Harrison, L., Shaw, R., Behbehani, G. K., Mardis, E. R., Miller, K., Venkata, L. P. R., Chang, H., Lee, D., Rosenthal, E., Kadauke, S., Bunin, N., Talano, J. A., Johnson, B., Wang, Y., & Cairo, M. S. (2023). Manufacture and characterization of good manufacturing practice-compliant SARS-COV-2 cytotoxic T lymphocytes. The Journal of Infectious Diseases, 227(6), 788–799.
Dudley, M. E., Wunderlich, J. R., Shelton, T. E., Even, J., & Rosenberg, S. A. (2003). Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. Journal of Immunotherapy, 26(4), 332–342.
Dudley, M. E., Wunderlich, J. R., Yang, J. C., Sherry, R. M., Topalian, S. L., Restifo, N. P., Royal, R. E., Kammula, U., White, D. E., Mavroukakis, S. A., Rogers, L. J., Gracia, G. J., Jones, S. A., Mangiameli, D. P., Pelletier, M. M., Gea-Banacloche, J., Robinson, M. R., Berman, D. M., Filie, A. C., Abati, A., & Rosenberg, S. A. (2005). Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. Journal of Clinical Oncology, 23(10), 2346–2357.
Dutcher, J. P., Schwartzentruber, D. J., Kaufman, H. L., Agarwala, S. S., Tarhini, A. A., Lowder, J. N., & Atkins, M. B. (2014). High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014. Journal for Immunotherapy of Cancer, 2(1), 26.
Eberlein, T. J., Rosenstein, M., & Rosenberg, S. A. (1982). Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. The Journal of Experimental Medicine, 156(2), 385–397.
Ernst, M., & Giubellino, A. (2022). The current state of treatment and future directions in cutaneous malignant melanoma. Biomedicine, 10(4).
Goff, S. L., Smith, F. O., Klapper, J. A., Sherry, R., Wunderlich, J. R., Steinberg, S. M., White, D., Rosenberg, S. A., Dudley, M. E., & Yang, J. C. (2010). Tumor infiltrating lymphocyte therapy for metastatic melanoma: Analysis of tumors resected for TIL. Journal of Immunotherapy, 33(8), 840–847.
Krishna, S., Lowery, F. J., Copeland, A. R., Bahadiroglu, E., Mukherjee, R., Jia, L., Anibal, J. T., Sachs, A., Adebola, S. O., Gurusamy, D., Yu, Z., Hill, V., Gartner, J. J., Li, Y. F., Parkhurst, M., Paria, B., Kvistborg, P., Kelly, M. C., Goff, S. L., Altan-Bonnet, G., Robbins, P. F., & Rosenberg, S. A. (2020). Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science, 370(6522), 1328–1334.
Mullinax, J. E., Egger, M. E., McCarter, M., Monk, B. J., Toloza, E. M., Brousseau, S., Jagasia, M., & Sarnaik, A. (2022). Surgical considerations for tumor tissue procurement to obtain tumor-infiltrating lymphocytes for adoptive cell therapy. Cancer Journal, 28(4), 285–293.
North, R. J. (1982). Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. The Journal of Experimental Medicine, 155(4), 1063–1074.
Radvanyi, L. G., Bernatchez, C., Zhang, M., Fox, P. S., Miller, P., Chacon, J., Wu, R., Lizee, G., Mahoney, S., Alvarado, G., Glass, M., Johnson, V. E., McMannis, J. D., Shpall, E., Prieto, V., Papadopoulos, N., Kim, K., Homsi, J., Bedikian, A., Hwu, W. J., Patel, S., Ross, M. I., Lee, J. E., Gershenwald, J. E., Lucci, A., Royal, R., Cormier, J. N., Davies, M. A., Mansaray, R., Fulbright, O. J., Toth, C., Ramachandran, R., Wardell, S., Gonzalez, A., & Hwu, P. (2012). Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clinical Cancer Research, 18(24), 6758–6770.
Rohaan, M. W., Borch, T. H., van den Berg, J. H., Met, O., Kessels, R., Geukes Foppen, M. H., Stoltenborg Granhoj, J., Nuijen, B., Nijenhuis, C., Jedema, I., van Zon, M., Scheij, S., Beijnen, J. H., Hansen, M., Voermans, C., Noringriis, I. M., Monberg, T. J., Holmstroem, R. B., Wever, L. D. V., van Dijk, M., Grijpink-Ongering, L. G., Valkenet, L. H. M., Torres Acosta, A., Karger, M., Borgers, J. S. W., Ten Ham, R. M. T., Retel, V. P., van Harten, W. H., Lalezari, F., van Tinteren, H., van der Veldt, A. A. M., Hospers, G. A. P., Stevense-den Boer, M. A. M., Suijkerbuijk, K. P. M., Aarts, M. J. B., Piersma, D., van den Eertwegh, A. J. M., de Groot, J. B., Vreugdenhil, G., Kapiteijn, E., Boers-Sonderen, M. J., Fiets, W. E., van den Berkmortel, F., Ellebaek, E., Holmich, L. R., van Akkooi, A. C. J., van Houdt, W. J., Wouters, M., van Thienen, J. V., Blank, C. U., Meerveld-Eggink, A., Klobuch, S., Wilgenhof, S., Schumacher, T. N., Donia, M., Svane, I. M., & Haanen, J. (2022). Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma. The New England Journal of Medicine, 387(23), 2113–2125.
Rosenberg, S. A., Eberlein, T. J., Grimm, E. A., Lotze, M. T., Mazumder, A., & Rosenstein, M. (1982). Development of long-term cell lines and lymphoid clones reactive against murine and human tumors: A new approach to the adoptive immunotherapy of cancer. Surgery, 92(2), 328–336.
Rosenberg, S. A., Spiess, P., & Lafreniere, R. (1986). A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science, 233(4770), 1318–1321.
Sarnaik, A. A., Hamid, O., Khushalani, N. I., Lewis, K. D., Medina, T., Kluger, H. M., Thomas, S. S., Domingo-Musibay, E., Pavlick, A. C., Whitman, E. D., Martin-Algarra, S., Corrie, P., Curti, B. D., Olah, J., Lutzky, J., Weber, J. S., Larkin, J. M. G., Shi, W., Takamura, T., Jagasia, M., Qin, H., Wu, X., Chartier, C., Graf Finckenstein, F., Fardis, M., Kirkwood, J. M., & Chesney, J. A. (2021). Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. Journal of Clinical Oncology, 39(24), 2656–2666.
Woroniecka, K. I., Rhodin, K. E., Dechant, C., Cui, X., Chongsathidkiet, P., Wilkinson, D., Waibl-Polania, J., Sanchez-Perez, L., & Fecci, P. E. (2020). 4-1BB agonism averts TIL exhaustion and licenses PD-1 blockade in glioblastoma and other intracranial cancers. Clinical Cancer Research, 26(6), 1349–1358.
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Johnson, J.E., Van Ryan, V.R., Dudek, A.Z. (2024). Tumor-Infiltrating Lymphocyte (TIL) Therapy. In: Dong, H., Markovic, S.N. (eds) The Basics of Cancer Immunotherapy. Springer, Cham. https://doi.org/10.1007/978-3-031-59475-5_4
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DOI: https://doi.org/10.1007/978-3-031-59475-5_4
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