Biography
Biography: Gilberto Filaci
Abstract
Telomerase, the enzyme synthesizing the telomeric regions of chromosomes, is considered as a universal tumor associated antigen because it is 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: the immunogenicity of telomerase; the capacity of telomerase vaccines of inducing clinical responses. The immunogenicity concerns have been now dispelled by demonstrations that: Telomerase is presented by tumor and antigen presenting cells; ex vivo generated telomerase-specific CTL kills efficiently telomerase-expressing tumors; circulating telomerase-specific T cells are present in 90% of cancer patients and, surprisingly, in 100% of healthy individuals, as observed in 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.