TCR-T Therapy Shows Antitumor Activity in HBV-Hepatocellular Carcinoma


Updated data were presented at the ISCT 2023 Meeting.

SCG Cell Therapy’s autologous HBsAg-specific T-cell receptor-engineered T Cell (TCR-T) therapy SCG101 has demonstrated antitumor activity in patients with Hepatitis B virus-hepatocellular carcinoma (HBV-HCC) treated in a phase 1/2 trial (NCT05417932).

Updated data from the trial were presented at the International Society for Cell & Gene Therapy (ISCT) conference in Paris, France, held May 31 to June 3, 2023.

"Tumor microenvironment plays a critical role in limiting the response to cancer immunotherapy. Targeting and clearance of HBsAg+ hepatocytes and HBV integrated premalignant dysfunctional cells would significantly contribute to SCG101 T cell stimulation and expansion before entering the hostile tumor microenvironment as well as modulating the immunosuppressive environment in the liver," said Ke Zhang, PhD, chief scientific officer, SCG Cell Therapy, said in a statement. "This unique property of SCG101 can effectively overcome a common challenge of T cell therapy, particularly for solid tumors.”

Patients treated with SCG101 experienced a median 74.5% tumor reduction after a single dose of SCG101 monotherapy. Patients had a duration of response of over 6.9 months at data cutoff. Investigators also performed pretreatment and post-treatment biopsies which showed 100% eradication of HBsAg+ hepatocytes in the liver. They also found reductions in serum HBsAg from 557.96 IU/mL at baseline to 1.3 IU/mL on Day 7 and then further reductions to 0.08 IU/mL (3.83 log reduction) by Day 28 after SCG101 infusion.

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Biomarker analyses revealed that a well-balanced CD8-CD4 ratio was observed after infusion as well as a persistent and high ratio of stem cell-like memory T-cells correlated with long-term T-cell proliferation. These biomarkers support prolonged T-cell function and sustained antitumor and antiviral responses.

"These exciting new data being presented at ISCT continue to reinforce the potential for viral antigen specific TCR-T cell therapy products to effectively treat infection-associated solid tumor indications like HBV-related hepatocellular carcinoma," Frank Wang, chief executive officer, SCG Cell Therapy, added. "Thus far, SCG101 has shown to produce robust and durable anti-tumor and antiviral responses and we look forward to providing additional updates on this program as the clinical trial progresses."

SCG101 specifically targets epitope peptide derived from Hepatitis B Surface Antigen (HBsAg) on HBV-HCC tumor cells, premalignant cells with HBV-DNA integration, and HBV-infected cells. The therapy, developed with SCG's proprietary GianT™ technology, is designed to trigger cytolytic and non-cytolytic mechanisms to eliminatethe targeted cells. SCG101 has previously shown antitumor activity and HBV cccDNA eradication in preclinical and clinical studies and has been cleared for clinical trials in the United States, China, and Singapore. The phase 1/2 trial is ongoing and is enrolling cohorts of 3-6 participants to evaluate each dose level for safety and tolerability in the dose-finding phase.

ISCT 2023: Late-breaking SCG101 data show 100% HBsAg+ hepatocyte eradication and 74.5% HCC tumour reduction with single dose HBsAg-specific TCR-T cell therapy. News release. SCG Cell Therapy. June 4, 2023.
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