TCR Redirected Therapy

Research Overview
The TCR Therapy Group is particularly interested to develop immune based therapies to reconstitute HBV-specific immunity in patients who are chronically infected or to target tumors expressing HBV antigens in patients with HBV-related hepatocellular carcinoma (HCC) since in these patients, HBV-specific T cells are functionally exhausted or deleted. Our approach is to genetically modify T cells by T cell receptor (TCR) gene transfer to generate new T cell responses that may supplement the deleted or functionally deficient HBV-specific T cells.

HBV-specific TCRs are cloned from T cells obtained from individuals with acute resolved HBV infection (that is likely to be associated with protection) and TCRs of known specificities are transferred to T cells from patients using retroviral transduction or messenger RNA (mRNA) electroporation. The functionality of TCR gene modified T cells to target HCC has been validated in vitro and in vivo in a HCC xenograft mouse model.

We are now working to translate the use of TCR gene modified T cells to the clinic for treatment of HBV-related HCC patients. In addition, we are actively working on engineering T cells that are able to inhibit HBV replication without causing hepatotoxicity, with the goal of using T cells with non-cytopathic antiviral activity for adoptive cell therapy in chronic HBV patients.