Telomerase as a universal tumor-associated antigen for cancer immunotherapy

Abstract

Although the search for pharmacologic inhibitors of telomerase activity represents a promising approach for telomerase-based anti-cancer therapy, the immunological properties of the telomerase reverse transcriptase hTERT suggest that the enzyme is also an attractive target for novel immunotherapies against cancer. Data from both human and murine systems demonstrate that cytotoxic T-lymphocytes (CTL) can recognize peptides derived from TERT and kill TERT-positive tumor cells of multiple histologies. Given the vast overexpression of hTERT in human tumors and its low-level expression in rare normal tissues, clinical trials have begun that test the credentials of hTERT as a broadly applicable target for immunotherapy of cancer.

Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma

“…In this sense, these results strongly suggest that serum anti-hTERT auto-antibodies would become a possible novel early tumor marker in hepatocellular carcinoma. Furthermore, since several groups have initiated vaccination strategies to induce anti-hTERT immunity, these studies suggest that cancer patients may well have on-going humoral immune responses to hTERT (Saeboe-Larssen et al, 2002;Treon et al, 2000;Vonderheide et al, 2001;Vonderheide, 2002).…”

Immunity against breast cancer by TERT DNA vaccine primed with chemokine CCL21

“…[5][6][7] TERT has been recognized as a potential TAA for cancerspecific immunotherapy. 8,9 TERT-specific CD4 þ or CD8 þ T cells have been induced in vitro from healthy donors or cancer patients. [10][11][12][13][14][15][16][17][18] However, effective anti-TERT-specific tumor immunity is difficult to induce in vivo consistently.…”

Targeting Adult and Pediatric Cancers via Cell-Based Vaccines and the Prospect of Activated B Lymphocytes as a Novel Modality

“…29,30 DC vaccination can safely induce T cell responses to self-antigens such as prostatic acid phosphatase (PAP), 31 idiotype protein, 24,32,33 melanoma antigens (such as MAGE-3, gp100, tyrosinase, and MART-1), [25][26][27] carcinoembryonic antigen, 28 prostate specific antigen, 34 mucin-1, 35 her2/neu, 35 prosate specific membrane antigen, 36 and telomerase. 37 DC loaded in a tumor-specific, but antigen unknown, fashion (such as with tumor lysate, peptides eluted from the surface of tumor cells, or tumor RNA 38,39 ) also appear to induce immune responses in patients. Antibody responses can also be elicited with DC vaccination, as seen with vaccines targeting the idiotype protein in B cell lymphoma.…”