Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells.

The polypeptide component of telomerase (TERT) is an attractive candidate f or a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against TERT induces immunity against tumors of unre lated origin. Immunization of mice with TERT RNA-transfected dendritic cell s (DC) stimulated cytotoxic T lymphocytes (CTL), which lysed melanoma and t hymoma tumor cells and inhibited the growth of three unrelated tumors in mi ce of distinct genetic backgrounds. TERT RNA-transfected human DC stimulate d TERT-specific CTL in vitro that lysed human tumor cells, including Epstei n Barr virus (EBV)-transformed B cells as well as autologous tumor targets from patients with renal and prostate cancer. Tumor RNA-transfected DC were used as surrogate targets in the CTL assays, obviating the difficulties in obtaining tumor cells from cancer patients. In one instance, where a tumor cell line was successfully established in culture from a patient with rena l cancer, the patient's tumor cells were efficiently lysed by the CTL. Immu nization with tumor RNA was generally more effective than immunization with TERT RNA, suggesting that an optimal immunization protocol may have to inc lude TERT as well as additional tumor antigens.