CD37-Targeting CAR Design for Antigen-Loss-Resistant Cancer Therapy

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Solution Overview

Problem

Current immunotherapies targeting CD19 and CD20 antigens on cancer cells can lead to relapse due to antigen loss, necessitating the development of alternative chimeric antigen receptors (CARs) that can target CD37, a protein highly expressed on immune cells, to effectively treat CD37+ cancers like lymphoma and leukemia.

Innovation Solution

Development of CAR polypeptides comprising a CD37-binding sequence, a transmembrane domain, and a T cell intracellular signaling domain, including CD3ζ, optionally with a co-stimulatory domain like 4-1BB, to redirect T-cell specificity towards CD37+ cells, enabling effective cancer treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CARs target CD19 or CD20 antigens on cancer cells, then cancer treatment effectiveness is improved, but antigen loss occurs leading to relapse

Engineering Contradiction:

Improvecancer treatment effectivenessVSAvoidantigen expression stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the target antigen parameter from CD19/CD20 to CD37, selecting a different molecular target that maintains therapeutic effectiveness while avoiding the antigen loss problem associated with previous targets

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The CAR construct combines multiple functional domains (extracellular antigen-binding domain, transmembrane domain, intracellular signaling domains including CD3ζ and co-stimulatory domains) to create a composite receptor that targets CD37 with enhanced effectiveness

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If CARs are designed to target CD37 on immune cells, then alternative cancer treatment is achieved, but risk of off-target effects on normal immune cells increases

Engineering Contradiction:

Improvetreatment alternative capabilityVSAvoidoff-target effects

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The CAR design incorporates specific local features including a precisely engineered extracellular domain that binds CD37 with high specificity, along with structured transmembrane and intracellular signaling domains that ensure targeted activation only upon CD37 binding

Inventive Principle:

Principle #3Local quality

Data Source

PatentEP3595721B1Chimeric antigen receptors targeting CD37

Publication Date: 2025.07.09 THE GENERAL HOSPITAL CORP

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AI summary

Described herein are chimeric antigen receptors (CARs) targeting CD37, as well as related molecules and methods.