Vaccines & Vaccination

Biography

Biography: Gilberto Filaci

Abstract

Telomerase, the enzyme synthesizing the telomeric regions of chromosomes, is considered a universal tumor associated antigen because expressed by the majority of cancers. The several clinical trials performed adopting telomerase as immunogen confirmed the safety of telomerase vaccination, but raised doubts concerning: a) the immunogenicity of telomerase; b) the capacity of telomerase vaccines of inducing clinical responses. The immunogenicity concerns have been now dispelled by demonstrations that: 1) telomerase is presented by tumor and antigen presenting cells; 2) ex vivo generated telomerase-specific CTL kill efficiently telomerase-expressing tumors; 3) circulating telomerase-specific T cells are present in 90% of cancer patients and, surprisingly, in 100% of healthy individuals, as observed in two our studies. These findings boost the search for a new generation of telomerase vaccines able to overcome the limits of their first generation. In this effort, our group recently completed a phase I/II trial in prostate and renal cancer patients with GX301, a new generation cancer vaccine. This multi-peptidic vaccine includes four telomerase peptides, which bind promiscuously several HLA class I and II alleles allowing the coverage of the majority of HLA haplotypes and the induction of both helper and cytotoxic T cell responses. It also contains two adjuvants with complementary activities, making it able to efficiently activate both innate and adoptive immune responses. The results of a phase I/II trial, showing a 100% rate of telomerase-specific immune responses associated with evidences of clinical responses, suggest that innovative approaches may lead telomerase (and cancer) vaccination to an "age of maturity".