Background: Hepatitis B virus (HBV) antigen expression frequently occurs in HBV-related hepatocellular carcinoma (HCC). We are performing a phase 1 trial to evaluate the safety and efficacy of activated autologous T cells, that express transiently an HBsAg/ HLA-class I restricted specific T cell receptor (HBV/TCR-T cell) trough mRNA TCR electroporation. . Here we report the first case of our trial. METHODS: The patient was given an intravenous injection of 4 doses of escalating HBV/TCR-T cell (1x104, 1x105, 1x106, and 5x106/kg) in the first treatment cycle, followed by a second treatment cycle of 4 doses of 5x106/kg one month later. The patient was evaluated every 8 weeks by radiologic imaging. Patients’ immune responses were monitored using an interferon-gamma enzyme-linked immunospot assay.
Results: The patient was a 41-year-old man with HBV associated HCC and undergone liver transplant at Jan 22nd, 2016. HCC relapse at the T12 thoracic vertebra was found 10 months after liver transplant, followed by a vertebral metastasis resection and radiotherapy. At 3 months after the resection, a new T9 metastasis was detected and treated with heavy ion radiotherapy once again. However, the serum α-fetoprotein (AFP) was increased from 167 to 2536 ng/ml and the tumor diameter increased from 3.6 to 5.8 cm within 4 months during the treatment. Then the first cycle of the HBV/TCR-T cell was given with serum HBV-DNA detected negative. The serum AFP drop from 2629 to 488 ng/ml after the first treatment cycle. However, the AFP was then gradually increased to 821 ng/ml after the second treatment cycle. HBV-DNA coding for HBV antigen was detected on the primary HCC. mRNA TCR-redirected T cells infusion was associated with a reduction in AFP levels without exacerbation of liver inflammation or other toxicity. During the HBV/TCR-T cell therapy, the metastasis tumor diameter was not increased without new lesions detected, which mean the disease stabilized in this case according to the Response Evaluation Criteria In Solid Tumors criteria. This clinical response continued for 5 months after the initiation of HBV/TCR-T cell therapy. We did not observe any serious adverse reactions to the immunotherapy, which was well tolerated.
Conclusion: We provide initial evidence of the safety and antitumor activity of autologous TCR-redirected immunotherapy in patients with recurrent hepatitis B-associated HCC after liver transplantation.