Fully Human Anti-B7H3 Antibody CAR-T Therapy for Solid Tumors
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Solution Overview
Problem
Current tumor therapies, such as surgery, chemotherapy, and radiotherapy, have limitations in effectively eradicating cancer cells due to infiltration and metastasis, while molecular targeted drugs face reduced efficacy with target gene mutations, and traditional immunotherapies struggle with immune system damage in cancer patients.
Innovation Solution
Development of a fully human anti-human B7H3 antibody and a fully human B7H3-targeting chimeric antigen receptor for genetically engineered immune cells, like CAR-T and iNKT cells, to enhance immune function and target tumor cells by overcoming immune checkpoint inhibition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional therapies (surgery, chemotherapy, radiotherapy) are used to treat tumors, then tumor cells can be removed to some extent, but complete eradication is failed due to infiltration and metastasis
Solution Approach 1:
The patent introduces chimeric antigen receptors (CARs) as intermediary molecules that mediate between immune cells and tumor cells. The CARs express specific antigen-binding domains (such as anti-B7H3 antibodies) that recognize tumor-specific antigens, enabling immune cells to selectively target and eliminate infiltrated and metastatic cancer cells that traditional therapies cannot reach.
Solution Approach 2:
The patent replaces traditional mechanical/physical tumor removal methods (surgery, radiotherapy) with a biological immune-based mechanism. By engineering immune cells to express CARs, the system uses biological recognition and cellular cytotoxicity instead of mechanical resection or radiation, enabling more comprehensive eradication of dispersed tumor cells.
2Reliability
If molecular targeted drugs are designed to act on specific gene mutant tumors, then specific carcinogenic sites can be targeted, but drug tolerance is generated when target tumor genes are mutated
Solution Approach 1:
The patent changes the targeting parameter from intracellular gene mutations to surface-expressed proteins (such as B7H3). By targeting extracellular proteins that remain stable even when underlying genes mutate, the therapy maintains efficacy across different tumor subtypes and mutation states, avoiding the drug tolerance issue associated with intracellular target mutations.
Solution Approach 2:
The patent creates a universal targeting approach using B7H3 as a common tumor-associated antigen expressed across multiple tumor types. The anti-B7H3 CARs can theoretically target various cancers expressing this protein, providing multi-functionality and broad adaptability that overcomes the limitation of mutation-specific targeted drugs.
3Reliability
If traditional immunotherapies are used to excite immune function, then tumor cell removal capacity can be enhanced, but immune system damage occurs in cancer patients
Solution Approach 1:
The patent applies local quality by directing immune activation to specific tumor locations through CAR expression on immune cells. The CARs ensure that immune cells only attack tumor cells expressing the target antigen (B7H3) while leaving normal tissues unaffected, thereby enhancing tumor removal capacity without causing widespread immune system damage.
Solution Approach 2:
The CAR acts as an intermediary that bridges the gap between general immune activation and specific tumor targeting. By equipping immune cells with CARs bearing specific antigen-binding domains, the system achieves targeted tumor recognition and elimination without the off-target effects and immune system damage associated with traditional immunotherapies.
4Measurement precision
If chimeric antigen receptors are designed with specific antibody components, then tumor targeting specificity is improved, but manufacturing complexity increases
Solution Approach 1:
The patent segments the CAR structure into distinct functional modules: antigen-binding domain (such as anti-B7H3 antibody fragments), transmembrane domain, and intracellular signaling domain. This segmentation allows for standardized production of each module and simplifies the overall manufacturing process while maintaining high targeting specificity through the modular antibody component.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The approach demonstrates strong proliferation, cytokine release, and killing capacity against solid tumor cells, offering a safe and effective method for tumor cell immunotherapy with high specificity and affinity for B7H3.
Implementation Method 1
The antibody or the antigen-binding fragment thereof specifically binds to B7H3
Implementation Method 2
The approach demonstrates strong proliferation, cytokine release, and killing capacity against solid tumor cells
Data Source
AI summary
Provided are a novel fully human antibody for human B7H3, a chimeric antigen receptor, and uses thereof; also provided are a novel fully human anti-human B7H3 antibody, a chimeric antigen receptor containing the antibody, and genetically engineered cells expressing the receptor and the antibody. It has been verified by experiments that CAR-T, CAR-NK and CAR-iNKT cells targeting B7H3 prepared on the basis of the present chimeric antigen receptor have relatively strong proliferation ability, cytokine release ability and tumor cell killing ability, and can effectively eliminate tumor cells.