Bispecific CAR T Cells Targeting CD13 and TIM-3 in AML

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Solution Overview

Problem

Current CAR T cell therapies for acute myeloid leukemia (AML) face challenges due to limited efficacy and side effects, as existing targets like CD33 and CD123 are not sufficiently effective, necessitating the development of novel approaches to enhance treatment outcomes.

Innovation Solution

Development of bispecific chimeric antigen receptors (CARs) that target both CD13 and TIM-3 on AML cells, utilizing antigen binding domains such as nanobodies and intracellular signaling domains like 4-1BB and CD3 zeta to enhance cytotoxicity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR T cell therapy targets CD33 or CD123, then some anti-leukemia activity is achieved, but side effects occur and efficacy is limited

Engineering Contradiction:

Improvetreatment efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent divides the antigen recognition function into two separate specificities within a single CAR structure. The bispecific CAR contains one antigen binding domain targeting CD13 and another targeting TIM-3, allowing the T cell to recognize and bind AML cells through dual specificity while sparing normal cells that may express only one of these markers

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a composite CAR structure that integrates multiple functional domains: CD13-specific antigen binding domain, TIM-3-specific antigen binding domain, transmembrane domain, and intracellular signaling domains (CD3 zeta, 4-1BB, CD28). This composite structure enables simultaneous recognition of two antigens and provides enhanced signaling for improved cytotoxicity

Inventive Principle:

Principle #40Composite materials

2Reliability

If single-specificity CARs are used, then the structure is simpler, but the ability to distinguish AML cells from normal cells is reduced

Engineering Contradiction:

Improvetargeting specificityVSAvoidCAR structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The CAR is segmented into distinct functional modules: an N-terminal CD13-specific scFv domain, a C-terminal TIM-3-specific scFv domain, separated by linkers and connected through a transmembrane domain to intracellular signaling regions. This segmentation allows each domain to independently contribute to antigen recognition while maintaining structural integrity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The bispecific CAR structure is designed to perform multiple functions simultaneously: recognizing CD13 on AML cells, recognizing TIM-3 on AML cells, providing co-stimulatory signals through 4-1BB and CD28 domains, and transducing activation signals through CD3 zeta. This multi-functionality enhances both specificity and efficacy

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250352582A1Compositions and methods for targeting CD13 and tim-3 with car t cells to treat acute myeloid leukemia

Publication Date: 2025.11.20 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

The present invention includes compositions and methods for treating AML utilizing bispecific CARs. In certain aspects, the invention includes a bispecific split CAR which binds CD13 and TIM-3 on AML cells.