Generating CAR T cells from tumor-infiltrating lymphocytes

从肿瘤浸润淋巴细胞产生 CAR-T 细胞

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作者:Jane K Mills, Melissa A Henderson, Lauren Giuffrida, Pasquale Petrone, Jennifer A Westwood, Phillip K Darcy, Paul J Neeson, Michael H Kershaw, David E Gyorki

Background

Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma.

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.

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.

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