SINGAPORE, July 12, 2023 /PRNewswire/ — SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, together with researchers from the University Medical Center Hamburg-Eppendorf and Technical University of Munich, received Best Presentation Award for the preclinical study of its first-in-class HBs-directed CD3 and CD28 bispecific antibodies – anti-HBs×CD3 and anti-HBs×CD28 – at the EASL Congress 2023. In the study presented, HBV-infected dual humanized mice received a combination of anti-HBs×CD3 and anti-HBs×CD28 antibodies, and after treatment, serum markers, including HBV DNA, HBsAg, and HBeAg, were significantly reduced.
A combination of anti-HBs×CD3 and anti-HBs×CD28 activated human lymphocytes in HBV-infected human liver chimeric mice and demonstrated potent in vivo antiviral efficacy. The data showed a significant reduction of all HBV markers, efficient recruitment of T cells to the liver, targeting of HBV-infected hepatocytes, and induction of both cytolytic and cytokine-mediated HBV-specific T cell immunity crucial for viral clearance. Levels of HBV pgRNA, HBV DNA, and cccDNA in the liver dropped significantly, consistent with the decrease of HBV serum parameters, indicating efficient clearance of infected hepatocytes.
“Specific re-direction of T cells to the infected hepatocytes in the liver triggering non-cytolytic control of HBV and killing HBsAg+ cells is curial to achieve a sustained HBV cure,” said Professor Ulrike Protzer, Director, Institute of Virology at Technical University of Munich / Helmholtz Munich and SCG Scientific Founder. “Treatment of HBV-infected humanized mice with our T-cell engager antibodies resulted in efficient recruitment of human CD4+ and CD8+ T cells into the liver and triggered an effective antiviral immune response”, she added.
“High levels of circulating HBsAg compromise antiviral immunity in chronic HBV carriers. Our approach demonstrates that T cells activated by antibodies can efficiently target the nuclear cccDNA reservoir despite high levels of baseline circulating HBsAg. Still, the permanently integrated viral DNA can also be targeted”, said Dr. Zhang Ke, Chief Scientific Officer of SCG.
Hepatitis B is the world’s most common liver infection. One in three humans experiences an HBV infection during their lifetime, and almost 300 million people are chronically infected worldwide. Approximately 25% of chronic HBV infections progress to liver cancer, and HBV contributes to an estimated 820,000 deaths annually. Despite commendable efforts in infant vaccination, about 1.5 million individuals contract new HBV infections yearly. Currently, there is no curative treatment available for HBV infection.
HBV-specific immune responses are the key to achieving HBV functional cure. To facilitate optimal local T-cell re-direction and activation, two novel T cell-engaging bispecific antibodies, anti-HBs×CD3 and anti-HBs×CD28, have been designed to bridge HBV-infected cells with CD3-expressing and CD28-expressing T cells. The rationale behind the combination of CD3 and CD28 bispecific antibodies stems from the requirement of T cells for dual signalling to achieve full activation. The initial “recognition” signal occurs when the T cell identifies a foreign antigen through its T-cell receptor/CD3 complex. However, activation of cytotoxic T-cell function only occurs upon receiving a secondary “costimulatory” signal, most effectively mediated by the CD28 costimulatory receptor. Anti-HBs×CD3 and anti-HBs×CD28 specifically target HBsAg with strong neutralizing functionality while bridging T cells to HBV-infected hepatocytes and concurrently providing activation through two crucial synergistic signals.
“Bispecific antibodies represent a novel and effective approach to treat certain cancers, and we believe this approach could more broadly apply to other disease areas, such as chronic infections. The publication showcases the significant impact of the anti-HBs×CD3 and anti-HBs×CD28 combination approach in driving substantially enhanced T-cell killing of HBV-infected cells, as demonstrated in these sophisticated dual-humanized animal models”, said Frank Wang, Chief Executive Officer of SCG. “The results from our first-in-class preclinical PoC study give us confidence in our bispecific development program for infectious diseases, and we eagerly anticipate further exploration and investigation.”
About SCG Cell Therapy
SCG is a leading biotechnology company focusing on developing novel immunotherapies for infections and their associated cancers. The company targets the most common cancer-causing infections: helicobacter pylori, human papillomavirus, and hepatitis B, and develops a broad and unique pipeline of T cell therapies, antibodies, and therapeutic vaccines against infections to prevent and cure its associated cancers. Established and headquartered in Singapore, SCG combines regional advantages in Singapore, China, and Germany, covering the entire value chain from innovative drug research and discovery manufacturing to clinical development and commercialization. For more information about SCG, please visit us at www.scgcell.com.