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Generating CAR T cells from tumor-infiltrating lymphocytes.

Authors :: Mills JK
Henderson MA
Giuffrida L
Petrone P
Westwood JA
Darcy PK
Neeson PJ
Kershaw MH
Gyorki DE
Source :: Therapeutic advances in vaccines and immunotherapy [Ther Adv Vaccines Immunother] 2021 May 31; Vol. 9, pp. 25151355211017119. Date of Electronic Publication: 2021 May 31 (Print Publication: 2021).
Publication Year :: 2021
Abstract: Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. Methods: We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Results: Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen. CAR-TIL produced greater amounts of IFN compared with parental TIL, when co-cultured with Her2 expressing tumor lines, including autologous melanoma tumor lines, although no consistent increase in cytotoxicity by TIL was afforded by expression of a CAR. Results of an in vivo study in NSG mice demonstrated tumor shrinkage when CAR-TILs were used in an adoptive cell therapy protocol. Conclusion: Potential limitations of transduced TIL in our study included limited proliferative potential and a terminally differentiated phenotype, which would need addressing in further work before consideration of clinical translation.<br />Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.<br /> (© The Author(s), 2021.)