Background
tumor, cancer, HCC, tumors, helper T-inducer
CANCERS, TUMOR, CANCER, TUMOR INITIATION, HUMAN PAPILLOMA VIRUS, HEPATOCELLULAR CARCINOMA, SECONDARY, TUMORS
Telomerase reactivation is observed in 90% of hepatocellular carcinoma (HCC) and seems to be a major step in tumor initiation [Several cancer immunotherapies that target the PD-L1/PD-1 pathway (The success of most immunotherapies relies on CD8We have elaborated a collaborative network to investigate the clinical impact of this Th1-inducer vaccine with atezolizumab in tumors where telomerase reactivation contributes to an oncogene addiction: human papilloma virus (HPV)-induced cancers and HCC. Our team has already promoted a phase II clinical trial (VolATIL study, NCT03946358 [Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cells expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Recent data from preclinical studies support this strategy. In conclusion, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC.So in the present TERTIO clinical trial, we propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with anti-PD-L1 therapy (atezolizumab) and bevacizumab in unresectable HCC by evaluation of the objective response rate at 6 months (randomized non-comparative phase II, 105 patients) according to RECIST v1.1 criteria. We will also decipher as a secondary objective, the molecular and immunological parameters determining the clinical outcomes.