CD276 Human Antibody Engineering for Safer Solid Tumor CAR-T
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Solution Overview
Problem
Current immunotherapies targeting CD276 for treating tumors face challenges such as the lack of suitable target antigens, short duration of CAR-T cells, immune escape, and immunosuppressive tumor microenvironments, leading to inefficacy in treating solid tumors, and mouse-derived antibodies cause human anti-mouse antibody reactions.
Innovation Solution
Development of fully humanized antibodies using human phage display library technology that specifically bind to CD276, enhancing antigen recognition and avoiding immune rejection, thereby improving the effectiveness and safety of CD276-CAR-T cell therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If mouse-derived antibodies are used for CD276 targeting, then antibody production is easier, but human anti-mouse antibody reactions occur causing rapid clearance
Solution Approach 1:
The patent changes the species origin parameter of the antibody from mouse-derived to fully humanized, transforming the antibody's biological properties to match human immune system characteristics, thereby eliminating HAMA reactions while maintaining CD276 targeting capability
Solution Approach 2:
The patent creates humanized versions of antibodies by copying and adapting the binding specificity from mouse-derived antibodies while replacing the antigen-binding sites with human sequences, producing antibodies that functionally replicate the original activity without triggering human immune rejection
2Reliability
If traditional chemotherapy is used for tumor treatment, then treatment effectiveness is achieved, but toxic side effects are high
Solution Approach 1:
The patent applies local quality by designing CAR-T cells with specific CD276-targeting antibodies that concentrate therapeutic activity only at tumor sites expressing CD276, rather than distributing systemic toxicity throughout the body, thereby achieving localized tumor killing with reduced off-target effects
Solution Approach 2:
The patent uses CD276 as an intermediary target protein that mediates between the therapeutic CAR-T cells and tumor cells, allowing selective engagement and killing of CD276-positive tumors while leaving CD276-negative cells unaffected, thus improving therapeutic index
3Reliability
If CAR-T cells are used for tumor treatment, then specific tumor cell killing is achieved, but duration in body is short
Solution Approach 1:
The patent applies preliminary action by pre-engineering CAR-T cells with optimized antibody receptors that enhance their survival and persistence capabilities before administration, so that they maintain functional activity in the body longer term rather than being rapidly cleared
Data Source
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AI summary
Provided are an antibody specifically binding to CD276 and use thereof. Specifically provided are a CD276 antibody or an antigen binding fragment thereof, and the like. Also provided are a polynucleotide encoding the CD276 antibody, a nucleic acid construct comprising the polynucleotide, an expression vector comprising the nucleic acid construct, a preparation method and a transformed cell thereof. The provided CD276 antibody can bind to CD276 protein at a high affinity and a high specificity, can be prepared into a target recognition domain of CAR-T cells, and can also be prepared into a bispecific T-cell engager (BiTE) to exert an anti-tumor effect for preventing or treating cancers.