TY  - JOUR
AU  - Du, S.*
AU  - Wisskirchen, K.*
AU  - Zhang, K.*
AU  - Protzer, U.
C1  - 72098
C2  - 56368
SP  - e44-e47
TI  - Correspondence on Editorial regarding "Genetically modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting".
JO  - Clin. Mol. Hepatol.
VL  - 31
IS  - 1
PY  - 2024
SN  - 2287-2728
ER  - 

TY  - JOUR
AB  - 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.
AU  - Wan, X.*
AU  - Wisskirchen, K.*
AU  - Jin, T.*
AU  - Yang, L.*
AU  - Wang, X.*
AU  - Wu, X.*
AU  - Liu, F.*
AU  - Wu, Y.*
AU  - Ma, C.*
AU  - Pang, Y.*
AU  - Li, Q.*
AU  - Zhang, K.*
AU  - Protzer, U.
AU  - Du, S.*
C1  - 70773
C2  - 55888
SP  - 735-755
TI  - Genetically redirected HBV-specific T cells target HBsAg-positive hepatocytes and primary lesions in HBV-associated HCC.
JO  - Clin. Mol. Hepatol.
VL  - 30
IS  - 4
PY  - 2024
SN  - 2287-2728
ER  -