Adoptive T-cell therapy as treatment for recurrent liver cancer after liver transplant: a pre-clinical development study

Project summary

An increasing indication for liver transplantation (LTx) is hepatocellular carcinoma (HCC).

Despite LTx, HCC often recurs, after which prognosis is dismal. Therefore, effective treatment is required to treat recurring tumors.

From an immunological point of view the post-transplant setting is of a particular interest since donor and recipient of the transplant liver have a different HLA-background. The objective of this pilot study, a collaboration between experienced onco-immunologists and clinicians, is to isolate T cell receptors (TCR) that are presented by recipient HLA expressed on residual tumor cells, which are of recipient origins. Such TCR will have a unique safety profile considering their inability to recognize the antigens on donor liver transplant tissue, which expresses donor HLA. In addition, the TCR cannot target other recipient organs because the selected antigens are exclusively expressed in the liver.

We aim to develop TCRs recognizing liver specific antigens in recipient but not donor HLA (LSARH) to be used to treat, and possibly in the future also prevent, recurrent HCC in patients after LTx. The expected outcome would have a number of TCR directed against LSARH that provide a starting point for an early phase clinical trial to treat patients with recurrent HCC following LTx.