1. Generating CAR T cells from tumor-infiltrating lymphocytes.
- Author
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Mills, JK, Henderson, MA, Giuffrida, L, Petrone, P, Westwood, JA, Darcy, PK, Neeson, PJ, Kershaw, MH, Gyorki, DE, Mills, JK, Henderson, MA, Giuffrida, L, Petrone, P, Westwood, JA, Darcy, PK, Neeson, PJ, Kershaw, MH, and Gyorki, DE
- 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.
- Published
- 2021