A Novel Anti-CD47 Nanobody Tetramer for Cancer Therapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• CD47 is overexpressed in tumors, promoting immune evasion via SIRPα interaction.
• Conventional monoclonal antibodies targeting CD47 have limitations in size and cost.
• Nanobodies offer a potential therapeutic alternative due to their unique properties.

Purpose of the Study:

• To engineer and characterize a high-affinity nanobody targeting the CD47-SIRPα axis.
• To evaluate the therapeutic potential of the anti-CD47 nanobody and its derivatives in cancer models.

Main Methods:

• Isolation of a VHH nanobody from an immunized alpaca phage library.
• Construction of a streptavidin-based tetramer nanobody derivative.
• In vitro and in vivo assays to assess phagocytosis, apoptosis induction, and efficacy.

Main Results:

• Engineered nanobody exhibits nanomolar affinity for SIRPα, surpassing the affinity of B6H12.2 antibody.
• Nanobody and derivatives effectively stimulate tumor cell phagocytosis and induce apoptosis in U937 cells.
• Demonstrated efficacy in both in vitro and in vivo cancer models.

Conclusions:

• The engineered anti-CD47 nanobody is a potent candidate for cancer immunotherapy.
• Nanobody-based therapeutics offer a more effective and cost-efficient approach to disrupt the CD47-SIRPα pathway.
• Potential for standalone or combinatorial use in oncology treatments.