Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals

Although high frequencies of T lymphocytes specific for certain tumor-assoc iated antigens have been detected in some cancer patients, increasing evide nce suggests that these T cells may be functionally defective in vivo and f ail to induce meaningful clinical responses. One strategy to overcome this limitation is to target novel antigens that are ignored during the natural antitumor immune response but are nevertheless capable of triggering effect or T-cell responses against tumors after optimal presentation by antigen-pr esenting cells. Here, we show that the telomerase catalytic subunit (hTERT) -a nearly universal tumor antigen identified by epitope deduction rather th an from patient immune responses-is immunologically ignored by patients des pite progressive tumor burden. Nevertheless, HLA-A2-restricted CTLs against hTERT are equivalently induced ex vivo from patients and healthy individua ls and efficiently kill human tumor cell lines and primary tumors. Thus, te lomerase-specific T cells from cancer patients are spared functional inacti vation because of immunological ignorance. These findings support clinical efforts to target the hTERT as a tumor antigen with broad therapeutic poten tial.