Breakthrough in Squamous Cell Carcinoma Treatment: Anti-B7-H3 Nanobody and DM1 Conjugate Show Promising Results

Strategic Insights -

Researchers at the University of Hong Kong-Shenzhen Hospital have made a significant breakthrough in the treatment of esophageal squamous cell carcinoma (ESCC), a highly aggressive malignancy with poor therapeutic outcomes. According to a recent study published in the International Journal of Biological Macromolecules, the team has developed a novel B7-H3-specific nanobody, BH1, which demonstrates subnanomolar binding affinity to a conformational epitope spanning the IgC1-IgV2 domains. When used in combination with DM1 conjugation, BH1-DM1 exhibits marked anti-tumor activity against ESCC, achieving 71.9% tumor growth inhibition.

Key Takeaways:

  • The study investigates the feasibility and efficacy of B7-H3 targeting using nanobodies and their drug conjugates as a therapeutic strategy for ESCC.
  • BH1, a novel B7-H3-specific nanobody, demonstrates subnanomolar binding affinity (EC = 2.32 nM) to a conformational epitope spanning the IgC1-IgV2 domains.
  • In vivo evaluation using KYSE30 xenograft models revealed rapid tumor-selective accumulation of BH1 within 4 h post-injection.
  • BH1 monotherapy inhibits tumor cell proliferation, induces G0/G1 phase arrest and apoptosis, achieving 37.7% tumor growth inhibition.
  • DM1 conjugation enhances the efficacy of BH1, achieving 71.9% suppression of tumor growth.
  • The research concludes that BH1-DM1 may offer a breakthrough therapeutic strategy for ESCC.

Statistics:

  • EC (binding affinity) of BH1 to B7-H3: 2.32 nM
  • Tumor growth inhibition with BH1 monotherapy: 37.7%
  • Tumor growth inhibition with BH1-DM1: 71.9%
  • Time for rapid tumor-selective accumulation of BH1: 4 h post-injection

Sources:

  • Anovel anti-B7-H3 nanobody and its DM1 conjugate with marked anti-tumor activity against esophageal squamous cell carcinoma. International Journal of Biological Macromolecules, 2025;322:147025.
  • Researchers at University of Hong Kong-Shenzhen Hospital Discuss Findings in Squamous Cell Carcinoma (Anovel anti-B7-H3 nanobody and its DM1 conjugate with marked anti-tumor activity against esophageal squamous cell carcinoma). Cancer Weekly. September 16, 2025; p 6277.