| Genetically redirected HBV-specific T cells target HBsAg-positive hepatocytes and primary lesions in HBV-associated HCC |
Xueshuai Wan1, Karin Wisskirchen2, Tao Jin2, Lu Yang2, Xiaorui Wang2, Xiang’an Wu1, Fang Liu1, Yu Wu1, Christy Ma2, Yong Pang2, Qi Li2, Ke Zhang2, Ulrike Protzer3
, Shunda Du1
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1Department of Liver Surgery, Peking Union Medical College Hospital, PUMC, and Chinese Academy of Medical Sciences
2SCG Cell Therapy Pte. Ltd.
3Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Munich, Munich, Germany. |
| Correspondence : |
Ulrike Protzer ,
Tel: 49-89-4140 6821, Fax: 49-89-4140 6823, Email: protzer@tum.de
Shunda Du ,
Tel: 86-10-69152836, Fax: 86-10-69156043, Email: dushd@pumch.cn
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Received: January 20, 2024 Revised: May 28, 2024 Accepted: May 28, 2024 |
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| ABSTRACT |
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Background and Aims
HBV-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it in an HBV-related HCC patient (NCT05339321).
Methods
GMP-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh:A, BCLC:B, ECOG:0, HBeAg-, serum HBsAg+, hepatocytes 10% HBsAg+) received 7.9x107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-hepatoma cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1404 U/ml, and concurrently, serum HBsAg started decreasing by 3.84log and remained <1 IU/ml for over six months. HBsAg expressing hepatocytes in liver biopsies were undetectable after73 days. The patient achieved a partial response according to mRECIST score with a >70% reduction of target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood.
Conclusions
SCG101 T-cell therapy showed encouraging efficacy and safety in pre-clinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing. |
| KeyWords:
HBV-induced HCC, adoptive cell therapy, chronic hepatitis B, immunotherapy, T cell receptor |
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