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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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Submitted January 19, 2005
Accepted October 7, 2005
Frequency of telomerase-specific CD8+ T lymphocytes in cancer patients
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
Department of Internal Medicine, University of Genoa, Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy; Center for Advanced Biotechnology, Genoa, Italy
Department of Internal Medicine, University of Genoa, Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy
Department of Internal Medicine, University of Genoa, Genoa, Italy
Urology Department, University of Genoa, Genoa, Italy
Institute Giannina Gaslini, Genoa, Italy
Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy
Department of Experimental Medicine, Biochemistry Section and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
Anatomic Pathology, San Martino Hospital, Genoa, Italy
The Department of Medicine and Cancer Center, University of California, San Diego, CA, USA
* Corresponding author; email: gfilaci{at}unige.it.
Telomerase is considered an universal tumor associated antigen 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 cancer patients. However, the data concerning frequency and functional activity of telomerase-specific CTL in cancer patients 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 HLA-A2+ cancer patients. The results show that the majority of cancer patients have circulating telomerasespecific CD8+ T lymphocytes, but high frequency of telomerase-specific CTL are present only in a fraction of them. Furthermore, CTL lines able to kill telomerase positive tumor cells, including autologous cancer cells, can be ex vivo expanded from some, but not all, cancer patients. In conclusion, the results of the study support the development of clinical protocols using telomerase peptides as immunizing agent. However, they underline the necessity to immunologically study single patients before undergoing vaccination, to select adequately the patients and to eventually adapt the immunization schedule to patient's immunologic status.
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