DOI QR코드

DOI QR Code

Engineered T Cell Receptor for Cancer Immunotherapy

  • So Won Lee (College of Pharmacy, Dongduk Women's University) ;
  • Hyang-Mi Lee (College of Pharmacy, Dongduk Women's University)
  • Received : 2023.11.07
  • Accepted : 2024.01.29
  • Published : 2024.07.01

Abstract

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant fund by the Korean government (MSIT) (No. 2022R1F1A1069379).

References

  1. Anderson, K. G., Voillet, V., Bates, B. M., Chiu, E. Y., Burnett, M. G., Garcia, N. M., Oda, S. K., Morse, C. B., Stromnes, I. M., Drescher, C. W., Gottardo, R. and Greenberg, P. D. (2019) Engineered adoptive T-cell therapy prolongs survival in a preclinical model of advanced-stage ovarian cancer. Cancer Immunol. Res. 7, 1412-1425.
  2. Blumenschein, G. R., Devarakonda, S., Johnson, M., Moreno, V., Gainor, J., Edelman, M. J., Heymach, J. V., Govindan, R., Bachier, C., Doger de Speville, B., Frigault, M. J., Olszanski, A. J., Lam, V. K., Hyland, N., Navenot, J., Fayngerts, S., Wolchinsky, Z., Broad, R., Batrakou, D., Pentony, M. M., Sanderson, J. P., Gerry, A., Marks, D., Bai, J., Holdich, T., Norry, E. and Fracasso, P. M. (2022) Phase I clinical trial evaluating the safety and efficacy of ADPA2M10 SPEAR T cells in patients with MAGE-A10(+) advanced non-small cell lung cancer. J. Immunother. Cancer 10, e003581.
  3. Chandran, S. S. and Klebanoff, C. A. (2019) T cell receptor-based cancer immunotherapy: emerging efficacy and pathways of resistance. Immunol. Rev. 290, 127-147.
  4. Doran, S. L., Stevanovic, S., Adhikary, S., Gartner, J. J., Jia, L., Kwong, M. L. M., Faquin, W. C., Hewitt, S. M., Sherry, R. M., Yang, J. C., Rosenberg, S. A. and Hinrichs, C. S. (2019) T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human, phase I/II study. J. Clin. Oncol. 37, 2759-2768.
  5. Ecsedi, M., McAfee, M. S. and Chapuis, A. G. (2021) The anticancer potential of T cell receptor-engineered T cells. Trends Cancer 7, 48-56.
  6. Hong, D. S., Van Tine, B. A., Biswas, S., McAlpine, C., Johnson, M. L., Olszanski, A. J., Clarke, J. M., Araujo, D., Blumenschein, G. R. J., Kebriaei, P., Lin, Q., Tipping, A. J., Sanderson, J. P., Wang, R., Trivedi, T., Annareddy, T., Bai, J., Rafail, S., Sun, A., Fernandes, L., Navenot, J., Bushman, F. D., Everett, J. K., Karadeniz, D., Broad, R., Isabelle, M., Naidoo, R., Bath, N., Betts, G., Wolchinsky, Z., Batrakou, D. G., Van Winkle, E., Elefant, E., Ghobadi, A., Cashen, A., Grand'Maison, A., McCarthy, P., Fracasso, P. M., Norry, E., Williams, D., Druta, M., Liebner, D. A., Odunsi, K. and Butler, M. O. (2023) Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial. Nat. Med. 29, 104-114.
  7. Hoppe-Seyler, K., Bossler, F., Braun, J. A., Herrmann, A. L. and Hoppe-Seyler, F. (2018) The HPV E6/E7 oncogenes: key factors for viral carcinogenesis and therapeutic targets. Trends Microbiol. 26, 158-168.
  8. Hoyos, V., Savoldo, B., Quintarelli, C., Mahendravada, A., Zhang, M., Vera, J., Heslop, H. E., Rooney, C. M., Brenner, M. K. and Dotti, G. (2010) Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 24, 1160-1170.
  9. Ishihara, M., Nishida, Y., Kitano, S., Kawai, A., Muraoka, D., Momose, F., Harada, N., Miyahara, Y., Seo, N., Hattori, H., Takada, K., Emori, M., Kakunaga, S., Endo, M., Matsumoto, Y., Sasada, T., Sato, E., Yamada, T., Matsumine, A., Nagata, Y., Watanabe, T., Kageyama, S. and Shiku, H. (2023) A phase 1 trial of NY-ESO-1-specific TCR-engineered T-cell therapy combined with a lymph node-targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma. Int. J. Cancer 152, 2554-2566.
  10. Jin, B. Y., Campbell, T. E., Draper, L. M., Stevanovic, S., Weissbrich, B., Yu, Z., Restifo, N. P., Rosenberg, S. A., Trimble, C. L. and Hinrichs, C. S. (2018) Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI Insight 3, e99488.
  11. June, C. H. and Sadelain, M. (2018) Chimeric antigen receptor therapy. N. Engl. J. Med. 379, 64-73.
  12. Leidner, R., Sanjuan Silva, N., Huang, H., Sprott, D., Zheng, C., Shih, Y., Leung, A., Payne, R., Sutcliffe, K., Cramer, J., Rosenberg, S. A., Fox, B. A., Urba, W. J. and Tran, E. (2022) Neoantigen T-cell receptor gene therapy in pancreatic cancer. N. Engl. J. Med. 386, 2112-2119.
  13. Lin, B., Du, L., Li, H., Zhu, X., Cui, L. and Li, X. (2020) Tumor-infiltrating lymphocytes: warriors fight against tumors powerfully. Biomed. Pharmacother. 132, 110873.
  14. Ma, S., Li, X., Wang, X., Cheng, L., Li, Z., Zhang, C., Ye, Z. and Qian, Q. (2019) Current progress in CAR-T cell therapy for solid tumors. Int. J. Biol. Sci. 15, 2548-2560.
  15. Mailankody, S., Devlin, S. M., Landa, J., Nath, K., Diamonte, C., Carstens, E. J., Russo, D., Auclair, R., Fitzgerald, L., Cadzin, B., Wang, X., Sikder, D., Senechal, B., Bermudez, V. P., Purdon, T. J., Hosszu, K., McAvoy, D. P., Farzana, T., Mead, E., Wilcox, J. A., Santomasso, B. D., Shah, G. L., Shah, U. A., Korde, N., Lesokhin, A., Tan, C. R., Hultcrantz, M., Hassoun, H., Roshal, M., Sen, F., Dogan, A., Landgren, O., Giralt, S. A., Park, J. H., Usmani, S. Z., Riviere, I., Brentjens, R. J. and Smith, E. L. (2022) GPRC5D-targeted CAR T cells for myeloma. N. Engl. J. Med. 387, 1196-1206.
  16. Majzner, R. G., Ramakrishna, S., Yeom, K. W., Patel, S., Chinnasamy, H., Schultz, L. M., Richards, R. M., Jiang, L., Barsan, V., Mancusi, R., Geraghty, A. C., Good, Z., Mochizuki, A. Y., Gillespie, S. M., Toland, A. M. S., Mahdi, J., Reschke, A., Nie, E. H., Chau, I. J., Rotiroti, M. C., Mount, C. W., Baggott, C., Mavroukakis, S., Egeler, E., Moon, J., Erickson, C., Green, S., Kunicki, M., Fujimoto, M., Ehlinger, Z., Reynolds, W., Kurra, S., Warren, K. E., Prabhu, S., Vogel, H., Rasmussen, L., Cornell, T. T., Partap, S., Fisher, P. G., Campen, C. J., Filbin, M. G., Grant, G., Sahaf, B., Davis, K. L., Feldman, S. A., Mackall, C. L. and Monje, M. (2022) GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 603, 934-941.
  17. Marofi, F., Motavalli, R., Safonov, V. A., Thangavelu, L., Yumashev, A. V., Alexander, M., Shomali, N., Chartrand, M. S., Pathak, Y., Jarahian, M., Izadi, S., Hassanzadeh, A., Shirafkan, N., Tahmasebi, S. and Khiavi, F. M. (2021) CAR T cells in solid tumors: challenges and opportunities. Stem Cell Res. Ther. 12, 81.
  18. Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E., Topalian, S. L., Kammula, U. S., Restifo, N. P., Zheng, Z., Nahvi, A., de Vries, C. R., Rogers-Freezer, L. J., Mavroukakis, S. A. and Rosenberg, S. A. (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126-129.
  19. Nagarsheth, N. B., Norberg, S. M., Sinkoe, A. L., Adhikary, S., Meyer, T. J., Lack, J. B., Warner, A. C., Schweitzer, C., Doran, S. L., Korrapati, S., Stevanovic, S., Trimble, C. L., Kanakry, J. A., Bagheri, M. H., Ferraro, E., Astrow, S. H., Bot, A., Faquin, W. C., Stroncek, D., Gkitsas, N., Highfill, S. and Hinrichs, C. S. (2021) TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat. Med. 27, 419-425.
  20. Phan, G. Q. and Rosenberg, S. A. (2013) Adoptive cell transfer for patients with metastatic melanoma: the potential and promise of cancer immunotherapy. Cancer Control 20, 289-297.
  21. Ramachandran, I., Lowther, D. E., Dryer-Minnerly, R., Wang, R., Fayngerts, S., Nunez, D., Betts, G., Bath, N., Tipping, A. J., Melchiori, L., Navenot, J., Glod, J., Mackall, C. L., D'Angelo, S. P., Araujo, D. M., Chow, W. A., Demetri, G. D., Druta, M., Van Tine, B. A., Grupp, S. A., Abdul Razak, A. R., Wilky, B., Iyengar, M., Trivedi, T., Winkle, E. V., Chagin, K., Amado, R., Binder, G. K. and Basu, S. (2019) Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma. J. Immunother. Cancer 7, 276.
  22. Rapoport, A. P., Stadtmauer, E. A., Binder-Scholl, G. K., Goloubeva, O., Vogl, D. T., Lacey, S. F., Badros, A. Z., Garfall, A., Weiss, B., Finklestein, J., Kulikovskaya, I., Sinha, S. K., Kronsberg, S., Gupta, M., Bond, S., Melchiori, L., Brewer, J. E., Bennett, A. D., Gerry, A. B., Pumphrey, N. J., Williams, D., Tayton-Martin, H. K., Ribeiro, L., Holdich, T., Yanovich, S., Hardy, N., Yared, J., Kerr, N., Philip, S., Westphal, S., Siegel, D. L., Levine, B. L., Jakobsen, B. K., Kalos, M. and June, C. H. (2015) NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat. Med. 21, 914-921.
  23. Restifo, N. P., Dudley, M. E. and Rosenberg, S. A. (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat. Rev. Immunol. 12, 269-281.
  24. Robbins, P. F., Kassim, S. H., Tran, T. L., Crystal, J. S., Morgan, R. A., Feldman, S. A., Yang, J. C., Dudley, M. E., Wunderlich, J. R., Sherry, R. M., Kammula, U. S., Hughes, M. S., Restifo, N. P., Raffeld, M., Lee, C. C., Li, Y. F., El-Gamil, M. and Rosenberg, S. A. (2015) A pilot trial using lymphocytes genetically engineered with an NYESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin. Cancer Res. 21, 1019-1027.
  25. Robbins, P. F., Morgan, R. A., Feldman, S. A., Yang, J. C., Sherry, R. M., Dudley, M. E., Wunderlich, J. R., Nahvi, A. V., Helman, L. J., Mackall, C. L., Kammula, U. S., Hughes, M. S., Restifo, N. P., Raffeld, M., Lee, C. R., Levy, C. L., Li, Y. F., El-Gamil, M., Schwarz, S. L., Laurencot, C. and Rosenberg, S. A. (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 29, 917-924.
  26. Rosenberg, S. A., Spiess, P. and Lafreniere, R. (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233, 1318-1321.
  27. Roth, T. L., Puig-Saus, C., Yu, R., Shifrut, E., Carnevale, J., Li, P. J., Hiatt, J., Saco, J., Krystofinski, P., Li, H., Tobin, V., Nguyen, D. N., Lee, M. R., Putnam, A. L., Ferris, A. L., Chen, J. W., Schickel, J., Pellerin, L., Carmody, D., Alkorta-Aranburu, G., Del Gaudio, D., Matsumoto, H., Morell, M., Mao, Y., Cho, M., Quadros, R. M., Gurumurthy, C. B., Smith, B., Haugwitz, M., Hughes, S. H., Weissman, J. S., Schumann, K., Esensten, J. H., May, A. P., Ashworth, A., Kupfer, G. M., Greeley, S. A. W., Bacchetta, R., Meffre, E., Roncarolo, M. G., Romberg, N., Herold, K. C., Ribas, A., Leonetti, M. D. and Marson, A. (2018) Reprogramming human T cell function and specificity with non-viral genome targeting. Nature 559, 405-409.
  28. Rudolph, M. G., Stanfield, R. L. and Wilson, I. A. (2006) How TCRs bind MHCs, peptides, and coreceptors. Annu. Rev. Immunol. 24, 419-466.
  29. Salter, A. I., Rajan, A., Kennedy, J. J., Ivey, R. G., Shelby, S. A., Leung, I., Templeton, M. L., Muhunthan, V., Voillet, V., Sommermeyer, D., Whiteaker, J. R., Gottardo, R., Veatch, S. L., Paulovich, A. G. and Riddell, S. R. (2021) Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function. Sci. Signal. 14, eabe2606.
  30. Schoutrop, E., El-Serafi, I., Poiret, T., Zhao, Y., Gultekin, O., He, R., Moyano-Galceran, L., Carlson, J. W., Lehti, K., Hassan, M., Magalhaes, I. and Mattsson, J. (2021) Mesothelin-specific CAR T cells target ovarian cancer. Cancer Res. 81, 3022-3035.
  31. Schultz-Thater, E., Piscuoglio, S., Iezzi, G., Le Magnen, C., Zajac, P., Carafa, V., Terracciano, L., Tornillo, L. and Spagnoli, G. C. (2011) MAGE-A10 is a nuclear protein frequently expressed in high percentages of tumor cells in lung, skin and urothelial malignancies. Int. J. Cancer 129, 1137-1148.
  32. Shafer, P., Kelly, L. M. and Hoyos, V. (2022) Cancer therapy with TCR-engineered T cells: current strategies, challenges, and prospects. Front. Immunol. 13, 835762.
  33. Shum, T., Omer, B., Tashiro, H., Kruse, R. L., Wagner, D. L., Parikh, K., Yi, Z., Sauer, T., Liu, D., Parihar, R., Castillo, P., Liu, H., Brenner, M. K., Metelitsa, L. S., Gottschalk, S. and Rooney, C. M. (2017) Constitutive signaling from an engineered IL7 receptor promotes durable tumor elimination by tumor-redirected T cells. Cancer Discov. 7, 1238-1247.
  34. Sun, Y., Li, F., Sonnemann, H., Jackson, K. R., Talukder, A. H., Katailiha, A. S. and Lizee, G. (2021) Evolution of CD8(+) T cell receptor (TCR) engineered therapies for the treatment of cancer. Cells 10, 2379.
  35. Weber, E. W., Maus, M. V. and Mackall, C. L. (2020) The emerging landscape of immune cell therapies. Cell 181, 46-62.
  36. Weiner, L. M., Murray, J. C. and Shuptrine, C. W. (2012) Antibody-based immunotherapy of cancer. Cell 148, 1081-1084.
  37. Xia, Y., Tian, X., Wang, J., Qiao, D., Liu, X., Xiao, L., Liang, W., Ban, D., Chu, J., Yu, J., Wang, R., Tian, G. and Wang, M. (2018) Treatment of metastatic non-small cell lung cancer with NY-ESO-1 specific TCR engineered-T cells in a phase I clinical trial: a case report. Oncol. Lett. 16, 6998-7007.
  38. Yarza, R., Bover, M., Herrera-Juarez, M., Rey-Cardenas, M., PazAres, L., Lopez-Martin, J. A. and Haanen, J. (2023) Efficacy of Tcell receptor-based adoptive cell therapy in cutaneous melanoma: a meta-analysis. Oncologist 28, e406-e415.
  39. Zhao, Y., Zheng, Z., Cohen, C. J., Gattinoni, L., Palmer, D. C., Restifo, N. P., Rosenberg, S. A. and Morgan, R. A. (2006) High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation. Mol. Ther. 13, 151-159.