Preclinical evaluation of adoptive cell therapy for patients with metastatic renal cell carcinoma.

Abstract

Interleukin-2 (IL-2) shows encouraging clinical results in metastatic renal cell carcinoma (RCC) patients, but is limited by substantial toxicity. Cell-based therapy holds a promise, but past attempts in RCC were unsuccessful. Advances in tumor-infiltrating lymphocytes (TIL) generation technology and modified clinical protocols recently yielded a 50% response in refractory melanoma patients.RCC-derived TIL and tumor cells were processed by current protocols from tumor specimens in a clean laboratory. The expanded TIL were characterized and tested in functional assays.The TIL cultures were efficiently generated and massively expanded. Virtually all the expanded cells were T-cells, but a considerable variability in the CD4/CD8 ratio and a frequent CD4-CD8-phenotype were observed. The TIL exerted cytotoxic or IFNgamma-release activities against autologous targets in major histocompatibility (MHC) class I-restricted and -independent functional patterns. The functional results were superior to former technologies.Recent developments in TIL generation technology and clinical patient conditioning protocols indicate that the TIL-based approach for RCC could be revisited.