Engineering T lymphocytes for chronic HBV infection immunotherapy

Immunotherapy based on adoptive transfer of T cells engineered to express HLA class I restricted T-cell receptor (TCR) or a chimeric antigen receptor (CAR) targeting tumor antigens has generated impressive results in treating some cancers. T cells are, however, also essential for the control of viral infections, particularly in persistent viral infections like HBV that is characterized by defect of antigen specific T cells.
We have built a library of virus-specific TCRs (mainly HBV-specific) that we use both in vitro and in vivo to engineer lymphocytes able to target both HBV infected hepatocytes and HBV-related liver tumor. However, while anti-cancer therapy seeks an efficient killing of cancer cells, antiviral therapy should maximize the suppression of viral replication with limited organ damage, particularly in viral infection targeting organs that are indispensable for life (as the liver).
I will discuss the strategies, such as time controlled TCR expression or modification of T cell function through the use on antisense nucleotides targeting T effector proteins, that are utilized in our laboratory to engineer antiviral lymphocytes with limited lysis ability for chronic viral infection treatment.