Anti-B7H3 Monoclonal Antibodies with Internalization and ADCC
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Solution Overview
Problem
Current treatments for cancer, particularly those targeting B7H3, face challenges in selectively inhibiting tumor cells while minimizing impact on normal tissues due to the similar expression levels of B7H3 in both normal and tumor tissues, leading to potential adverse effects on healthy cells.
Innovation Solution
Development of a group of anti-B7H3 monoclonal antibodies with high affinity and specificity, capable of cellular internalization, ADCC, and toxin conjugation, along with humanized variants, to selectively target and inhibit tumor cells while reducing impact on normal tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-B7H3 antibodies are used to target tumor cells, then tumor cell inhibition is improved, but normal tissues are also affected due to similar B7H3 expression levels
Solution Approach 1:
The patent develops antibodies with different functional properties (internalization capability, ADCC activity, toxin conjugation) to create localized therapeutic effects. By selecting antibodies that can be internalized or conjugated with toxins, the treatment can selectively affect tumor cells while sparing normal tissues that express similar B7H3 levels but lack these additional functional characteristics.
Solution Approach 2:
The patent modifies the antibody properties by humanizing them and creating variants with different functional capabilities. This allows tuning of the therapeutic index by selecting antibodies that maintain high affinity for B7H3 while acquiring additional functions (internalization, ADCC) that enhance tumor selectivity and reduce normal tissue toxicity.
2Measurement precision
If high affinity anti-B7H3 antibodies are developed, then binding specificity is improved, but selectivity between tumor and normal cells deteriorates due to ubiquitous B7H3 expression
Solution Approach 1:
The patent combines high-affinity B7H3 binding with additional functional properties in the same antibody molecule. By merging binding specificity with internalization capability or ADCC activity, the antibody achieves both high specificity for B7H3 and functional selectivity for tumor cells, overcoming the limitation of ubiquitous B7H3 expression.
Solution Approach 2:
The patent creates composite therapeutic agents by conjugating high-affinity antibodies with toxins or utilizing their ability to recruit immune cells. This composite approach allows the antibody to serve dual purposes: specific binding to B7H3 and selective delivery of therapeutic effect to tumor cells through mechanisms like toxin internalization or ADCC.
Data Source
AI summary
Provided are a group of anti-B7H3 monoclonal antibodies and humanized antibodies thereof. The antibodies obtained by means of hybridoma technology have B7H3 affinity, cell endocytosis effect, and antibody-dependent cytotoxicity, or can effectively block an immunosuppressive effect caused by B7H3, and can be used for preparing related drugs for inhibiting cancer cells, regulating the effect and level of B7H3, and enhancing the immunity of an organism.