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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1505-1512.
Prepublished online as a Blood First Edition Paper on October 25, 2005; DOI 10.1182/blood-2005-01-0258.
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IMMUNOBIOLOGY
Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer
Gilberto Filaci,
Marco Fravega,
Maurizio Setti,
Paolo Traverso,
Enrico Millo,
Daniela Fenoglio,
Simone Negrini,
Francesca Ferrera,
Andrea Romagnoli,
Monica Basso,
Paola Contini,
Marta Rizzi,
Massimo Ghio,
Umberto Benatti,
Gianluca Damonte,
Jean Louis Ravetti,
Giorgio Carmignani,
Maurizio Zanetti, and
Francesco Indiveri
From the Departments of Internal Medicine; Urology; Experimental Medicine, Biochemistry Section; and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Italy; Center of Advanced Biotechnology, Genoa, Italy; Institute Giannina Gaslini, Genoa, Italy; Department of Anatomic Pathology, San Martino Hospital-Genoa, Italy; and the Department of Medicine and Cancer Center, University of California at San Diego, La Jolla, CA.
Telomerase is considered a universal tumor-associated antigen (TAA) due to its high rate of expression by cancers ( 90%), and clinical trials are in progress to test the immunotherapeutical efficacy of antitelomerase immunization in patients with cancer. However, the data concerning frequency and functional activity of telomerase-specific cytotoxic T lymphocytes (CTLs) in patients with cancer are few and conflicting, although their knowledge would be mandatory to predict the efficacy of telomerase-specific immunotherapy in selected patients. We performed this study to analyze frequency and cytolytic function of circulating CD8+ T lymphocytes specific for the p540 telomerase peptide in a series of human leukocyte antigen (HLA)–A2+ cancer patients. The results show that most patients with cancer have circulating telomerase-specific CD8+ T lymphocytes, but a high frequency of telomerase-specific CTLs are present only in a fraction of them. Furthermore, CTL lines able to kill telomerase-positive tumor cells, including autologous cancer cells, can be expanded ex vivo from some, but not all, patients with cancer. In conclusion, the results of the study support the development of clinical protocols using telomerase peptides as an immunizing agent. However, they underline the necessity to study single patients immunologically before undergoing vaccination, to select the patients adequately, and to eventually adapt the immunization schedule to the patient's immunologic status.
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