AAV vectors in the context of gene therapy and as a promising new player in the immunotherapies of cancer

Summary:

AAV vectors are effective and safe viral vectors, and have become the leading platform for human gene therapy, with 7 AAV-based therapies approved by the EMA/FDA agencies.

However, in the context of gene therapy, immune responses against the capsid and the transgene product remain major limitations that restrain their long-term therapeutic efficacy. In addition to conventional immunosuppression regimens, several approaches aim to induce antigen-specific tolerance. We will briefly summarize our work and the prospects offered by these immunoregulation protocols.

In the long road to improve cancers treatments, several recent trials aim to administer AAV vectors inside the tumor bed, in order to promote significant modification of the tumor microenvironment and anti-tumor immune responses. We will present our work in this direction, using AAV vectors encoding pyroptotic inducers (which promote immunogenic cell death), cytokines, or immunocytokines. Intratumoral injections of AAV vectors, in combination with other approved immunotherapies, represent an exciting new prospect for increasing tumor immunogenicity and promoting tumor rejection.

Biosketch:

Pr Sahil Adriouch, has obtained his PhD in 2003 from University Diderot (Paris 7) and his habilitation to supervise and conduct research in 2014. Pr S. Adriouch is a Professor of Immunology and Biotherapy in the medical faculty of the University of Rouen-Normandy and an active member of Inserm unit U1235, hosted by the institute for Research and Biomedicine (IRIB). He has a recognized expertise in Immunoregulation (Immune checkpoints, biology of regulatory T cells, regulation of the immune system by P2X7 and other members of the purinergic pathway, regulation of innate and adaptive immune responses). Pr S Adriouch has also recently gained experience in the field of gene therapy, in the development of viral vectors such as rAAV, and in the immune responses that they induce. In the most recent project, Pr S Adriouch has developed project related to the use of AAV vectors to increase immune responses in the context of cancer, and to promote tumor rejections.