Multispecific CAR-T and T-Cell Engager for Solid Tumor Killing

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Solution Overview

Problem

Current cancer immunotherapies using chimeric antigen receptors (CAR) and bispecific T-cell engagers (BiTE) are effective for hematological malignancies but show limited efficacy in treating solid tumors, highlighting the need for improved therapeutic targets and strategies.

Innovation Solution

Development of a multispecific single domain antibodies chimeric antigen receptor and T-cell engager, comprising an HLA-G single domain antibody and a bispecific T-cell engager that targets HLA-G and PD-L1, linked to a CD3z signaling domain, to enhance immune cell cytotoxicity against tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR or BiTE immunotherapy is used, then hematological malignancies are effectively treated, but solid tumors show limited therapeutic response

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidapplicability to different tumor types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a multispecific CAR structure that can simultaneously recognize multiple antigens (including HLA-G and other solid tumor-associated antigens) while maintaining the CD3ζ signaling domain for T-cell activation. This multi-functional design allows the same CAR construct to be effective against both hematological malignancies and solid tumors, resolving the contradiction between therapeutic reliability and adaptability to different tumor types

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Productivity

If single-specific CAR or BiTE is used, then antigen recognition is achieved, but tumor cell killing efficiency is insufficient

Engineering Contradiction:

Improvetumor cell killing efficiencyVSAvoidreceptor structure complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent merges multiple antigen recognition domains into a single CAR construct, creating a multispecific receptor that combines multiple single-domain antibody units with the CD3ζ signaling domain. This consolidation approach increases tumor cell killing efficiency by enabling simultaneous recognition of multiple antigens while maintaining manageable structural complexity through modular design

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The CAR construct functions as a composite molecular structure combining different functional elements: single-domain antibody recognition units, transmembrane domains, and CD3ζ signaling domains. This composite design enhances tumor cell killing efficiency by integrating multiple functions into one receptor while keeping the overall structure organized and manageable

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS12509519B2Multispecific single domain antibodies chimeric antigen receptor and T-cell engager, nucleic acid, expressing cell thereof, pharmaceutical composition for treating cancer, and method for inhibiting proliferation of tumor cell

Publication Date: 2025.12.30 EVER SUPREME BIO TECH CO LTD

AI summary

A multispecific single domain antibodies chimeric antigen receptor and T-cell engager includes an HLA-G single domain antibody chimeric antigen receptor and a bispecific T-cell engager. The HLA-G single domain antibody chimeric antigen receptor includes an HLA-G single domain antibodies unit, a transmembrane domain, and a CD3z signaling domain. The bispecific T-cell engager includes a PD-L1 single domain antibodies unit and a CD3e single domain antibody.