title: Preventive vaccination with telomerase controls tumor growth in genetically engineered and carcinogen-induced mouse models of cancer.
abstract: The telomerase reverse transcriptase, TERT, is an attractive target for human cancer vaccination because its expression is reactivated in a conspicuous fraction of human tumors. Genetic vaccination with murine telomerase (mTERT) could break immune tolerance in different mouse strains and resulted in the induction of both CD4+ and CD8+ telomerase-specific T cells. The mTERT-derived immunodominant epitopes recognized by CD8+ T cells were further defined in these mouse strains and used to track immune responses. Antitumor efficacy of telomerase-based vaccination was investigated in two cancer models closely resembling human diseases: the TRAMP transgenic mice for prostate cancer and a carcinogen-induced model for colon cancer. TERT overexpression in tumor lesions was shown in both models by immunohistochemistry, thus reinforcing the similarity of these tumors to their human counterparts. Repeated immunizations with mTERT-encoding DNA resulted in a significant delay of tumor formation and progression in both the prostate cancer and the colon cancer models. Moreover, evaluation of the intratumoral infiltrate revealed the presence of telomerase-specific T cells in vaccinated mice. The safety of vaccination was confirmed by the absence of histomorphologic changes on postnecropsy analysis of several organs and lack of adverse effects on blood cell counts. These results indicate that TERT vaccination can elicit antigen-specific immunosurveillance and imply this antigen as a potential candidate for preventive cancer vaccines.
authors.affiliation: Istituto di Ricerca di Biologia Molecolare, Pomezia, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Mennuni
authors.forename: Stefano
authors.initials: S
authors.lastname: Ugel
authors.forename: Federica
authors.initials: F
authors.lastname: Mori
authors.forename: Barbara
authors.initials: B
authors.lastname: Cipriani
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Tania
authors.initials: T
authors.lastname: Pannellini
authors.forename: Domenico
authors.initials: D
authors.lastname: Lazzaro
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.forename: Elisa
authors.initials: E
authors.lastname: Scarselli
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005818:Genetic Engineering; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control; D019098:Telomerase / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D019098:Telomerase; C509187:Tert protein, mouse