A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation

Hepatocellular carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 10 patients with Hepatitis B virus (HBV) related HCC who underwent liver transplantation and are confirmed to have recurrent HCC. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.

Sex

All

Minimum age

21 Years

Maximum age

65 Years

Inclusion Criteria:

* Diagnosis as hepatocellular carcinoma (HCC)
* Underwent liver transplantation and confirmed recurrent HCC post operation
* Seropositive for hepatitis B surface antigen
* No major post-operative complication
* Life expectancy of at least 12 weeks
* Ability to provide informed consent
* Ability to comply with study procedures
* HLA profile matching with HLA-class I restriction element of the available T cell receptors

Exclusion Criteria:

* Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR-T, stem cells or combined therapy of the kind within 3 months prior to enrolment
* Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
* Likelihood to require steroid treatment during the period of the clinical trial
* Any other concurrent liver infections such as hepatitis A, C or D infection
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
* Known Central Nervous System tumours including metastatic brain disease.
* Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
* Patients with reproductive potential who tested positive for serum or urine pregnancy test result within 14 days prior to enrolment.

• BACKGROUNDQasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13. PMID 25308176
• BACKGROUNDGehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23. PMID 21145860
• BACKGROUNDKoh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43. PMID 23941866
• DERIVEDYang F, Zheng X, Koh S, Lu J, Cheng J, Li P, Du C, Chen Y, Chen X, Yang L, Chen W, Wong RW, Wai LE, Wang T, Zhang Q, Chen W. Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial. Hepatol Int. 2023 Aug;17(4):850-859. doi: 10.1007/s12072-023-10524-x. Epub 2023 Apr 17. PMID 37067675