Multivalent VHH Binding Agents for CD36 Tumor Targeting
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Solution Overview
Problem
Existing VHH-based therapeutics face challenges with limited half-life and potential immunogenicity, and CD36 plays a significant role in tumor metastasis and treatment resistance, necessitating improved targeting strategies for cancer treatment.
Innovation Solution
Development of binding agents comprising single domain antibodies that target CD36, PD-1, and/or CD47, which can inhibit tumor growth, metastasis, and resistance to chemotherapeutics by modulating lipid metabolism and immune checkpoint interactions, utilizing polypeptide chains with antigen binding domains to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If VHH-based therapeutics are used to target tumor cells, then tumor targeting capability is improved, but half-life is limited and renal clearance increases
Solution Approach 1:
The patent combines multiple VHH units into multivalent constructs (bivalent, trivalent, or multimeric forms) to increase avidity and affinity for tumor cells. This merging approach enhances targeting reliability while the multivalent structure also provides prolonged circulation time by reducing renal clearance through increased molecular size, thus resolving the half-life limitation without compromising targeting capability.
2Duration of action of moving object
If conventional antibodies are used to extend VHH half-life, then therapeutic efficacy is improved, but immunogenicity increases
Solution Approach 1:
Instead of using conventional antibodies that extend half-life but increase immunogenicity, the patent employs engineered VHH-based multivalent constructs that achieve prolonged circulation through multimerization and Fc fusion strategies. These engineered proteins maintain human sequence identity (>85%) to reduce immunogenicity while achieving extended half-life through controlled multivalent architecture rather than relying on non-human antibody structures.
3Reliability
If CD36 targeting is used to inhibit tumor growth, then therapeutic efficacy is improved, but tumor metastasis and treatment resistance mechanisms remain active
Solution Approach 1:
The patent creates multispecific binding agents that simultaneously target CD36 (to inhibit lipid metabolism and tumor growth) and other tumor-associated antigens or immune checkpoint molecules. This multi-functionality allows a single therapeutic agent to address multiple cancer hallmarks including growth inhibition, metastasis prevention, and treatment resistance overcoming, thereby resolving the contradiction between therapeutic efficacy and harmful tumor mechanisms.
Data Source
AI summary
The present disclosure generally relates to binding agents that are capable of targeting tumor cells and/or immune cells and their use for treating cancer. The binding agents of the present disclosure comprise one or more antigen binding domains of single domain antibodies which are capable of binding to Cluster of Differentiation 36 (CD36), to Programmed Cell Death protein 1 (PD-1) and/or to Cluster of Differentiation 47 (CD47). The binding agents of the present disclosure are monospecific or multispecific and may be in the form of monomers or multimers.