Engineered Nanobody Chimeras Recruits Anti-HBV Antibodies for Target Cancer Immunotherapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Monoclonal antibodies (mAbs) face challenges in cost, accessibility, and immunogenicity for cancer immunotherapy.
• Hepatitis B virus (HBV) vaccination induces endogenous antibodies that could potentially be repurposed.

Purpose of the Study:

• To explore redirecting endogenous anti-HBV antibodies towards cancer cells for immunotherapy.
• To engineer a bifunctional nanobody chimera for this purpose.

Main Methods:

• Engineered a 7D12-HBsAg(99-169) nanobody chimera combining anti-EGFR and HBV surface antigen domains.
• Tested the chimera's ability to recruit anti-HBV antibodies to cancer cells.
• Assessed antibody-dependent cell-mediated phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC).
• Evaluated tumor growth inhibition in a xenograft mouse model.

Main Results:

• The nanobody chimera successfully recruited endogenous anti-HBV antibodies to EGFR-positive cancer cells.
• This recruitment triggered potent ADCP and CDC, leading to selective cancer cell killing.
• The 7D12-HBsAg(99-169) fusion significantly inhibited tumor growth in mice without notable toxicity.

Conclusions:

• This study provides a proof-of-concept for using vaccine-induced endogenous antibodies in cancer immunotherapy.
• Leveraging HBV vaccination-generated antibodies offers a novel and potentially accessible approach for cancer treatment.