Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed by primary and metastatic tumors

Although renal cell carcinoma has been shown to respond to immunotherapy, r enal cell carcinoma-specific rejection antigens and their corresponding CTL epitopes have rarely been described. The use of dendritic cells (DCs) tran sfected with mRNA isolated from tumor cells may allow specific immunotherap y even in cancers for which potent rejection antigens have not been identif ied, Here me show that DCs transfected with RNA isolated from renal cancer tissue are remarkably effective in stimulating tumor-specific T-cell respon se in vitro but do not cross-react with normal tissue antigens including an tigens expressed by renal parenchyma. In contrast, the tumor-specific CTLs lysed allogeneic tumor but not allogeneic normal tissue targets, suggesting the presence of shared albeit unidentified antigens among renal carcinomas . CTL responses against telomerase reverse transcriptase (TERT) accounted i n part for the reactivities against allogeneic tumors because renal tumor R NA-transfected DCs stimulated polyclonal CTL responses,,which encompassed a s a subcomponent a response against TERT, Nonetheless, the tumor-specific C TLs were consistently superior to the CTLs stimulated with TERT RNA transfe cted DCs in recognizing and lysing tumor targets, suggesting that tumor-spe cific CTLs represent a polyclonal response providing more effective antitum or activity than T-cell responses directed against a single antigen in the form of TERT, Tumor RNA-transfected DCs mere capable of stimulating T-cell reactivities not only against the primary tumor but also against metastatic tumors, although discrete differences in the antigenic repertoire expresse d by these tissues were apparent. Thus, total tumor RNA-transfected DCs may represent a broadly applicable vaccine strategy to induce polyclonal and p otentially therapeutic T cell responses in renal cancer patients.