B7-H3 Binders for Solid Tumor CAR T Targeting

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Solution Overview

Problem

Existing immunotherapy approaches for solid tumors, particularly pediatric solid tumors, face challenges due to the absence of suitable antigen targets and hostile immunological microenvironments, limiting the effectiveness of CAR T cell technology.

Innovation Solution

Development of novel antigen binding molecules, such as scFvs and CARs, specifically targeting B7-H3 with identified CDR sequences, which demonstrate superior antigen-specific cytotoxicity and cytokine secretion, and their application in antibody-drug conjugates and multispecific antigen binding molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR T cell technology is used for solid tumors, then treatment approach is established, but effectiveness is limited due to absence of suitable antigen targets and hostile microenvironment

Engineering Contradiction:

Improveeffectiveness of CAR T cell therapyVSAvoidsuitability for solid tumor targets

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the antigen target parameter from conventional solid tumor markers to B7-H3, which is selectively expressed on tumor cells but not on normal tissues. This parameter change enables effective targeting of solid tumors while avoiding the hostile microenvironment problem, as B7-H3 is absent from normal cells including those in the microenvironment.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses scFv fragments that copy the binding specificity of full monoclonal antibodies against B7-H3. These scFv-based CARs replicate the successful targeting capability of antibody therapy while maintaining the advantages of CAR T cell technology for solid tumor treatment.

Inventive Principle:

Principle #26Copying

2Measurement precision

If B7-H3 is used as target antigen, then tumor specificity is improved, but understanding of signaling mechanism remains incomplete

Engineering Contradiction:

Improvespecificity of B7-H3 targetingVSAvoidsignaling mechanism knowledge

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent extracts the essential function of B7-H3 targeting from the complex signaling mechanism question. By focusing on the extracellular domain binding interface and using scFv fragments, the invention achieves high-specificity targeting without requiring complete understanding of the intracellular signaling pathways, thus separating the targeting function from the signaling mechanism.

Inventive Principle:

Principle #2Taking out (Extraction)

3Ease of manufacture

If existing scFv binders are used, then clinical translation is possible, but anti-tumor reactivity and cytokine secretion are insufficient

Engineering Contradiction:

Improveclinical translation capabilityVSAvoidanti-tumor reactivity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent optimizes the scFv binders by changing parameters such as affinity, specificity, and structural configuration. The novel scFv fragments exhibit enhanced binding affinity to B7-H3 and improved anti-tumor reactivity compared to existing binders, while maintaining the simplicity of scFv-based CAR construction for clinical translation.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250382369A1B7h3 binders

Publication Date: 2025.12.18 UCL BUSINESS LTD

AI summary

The present invention relates to novel antigen binding molecules which specifically bind to B7H3. The invention also relates to chimeric antigen receptors (CARs) and antibody-drug conjugates (ADCs) comprising the antigen binding molecules. Also provided are uses of the antigen binding molecules, CARs and ADCs, and pharmaceutical compositions comprising the antigen binding molecules, CARs and ADCs.