Viral vectored vaccines for prostate cancer

New therapeutic antigen-specific approaches are required to generate and sustain therapeutic immune responses against tumour specific antigens in cancer Based on twenty years of experience with attempt to maximise the induction of potent T cell responses against infectious pathogens in humans we have begun to assess the utility of non-replicating viral vectors in cancer Two trials in prostate cancer patients have completed enrolment and another in lung cancer is planned We have reported efficacy data for a novel vaccine based on two replication-deficient viruses, chimpanzee adenovirus (ChAdOx1) and MVA, targeting an oncofetal self-antigen 5T4, administered as a single agent and in combination with anti-PD-1 in mouse tumour models Based on recently reported encouraging safety and exceptional T cell immunogenicity in a phase I "VANCE" study (NCT02390063) of me with localised prostate cancer, the phase I/II trial, ADVANCE (NCT03815942) was undertaken to test vaccine safety and efficacy in combination with PD-1 blockade in metastatic prostate castrate-resistant cancer (mCPRC) We find a satisfactory safety profile for the use of these viral vectored vaccines with anti-PD1 in mCRPC patients but with lower immunogenicity than in localised prostate cancer patients However, an encouraging response rate, as measured the reduction in PSA levels by 50%, was observed in this trial and options for enhancing immunogenicity and efficacy further will be discussed