Modular Chimeric Antigen Receptors for Switchable Multi-Marker Targeting

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Solution Overview

Problem

Traditional CAR-T therapies lack flexibility, activating the immune system immediately upon cancer cell recognition and are limited to recognizing a single marker, requiring multiple CARs for multiple markers and lacking the ability to adjust marker recognition post-administration.

Innovation Solution

The recognition and signaling portions of the CAR are separated into distinct polypeptides, allowing for modular and flexible CAR-T therapy where the recognition polypeptides can be administered separately from the signaling polypeptides, enabling control over immune activation and switching between markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional CAR-T cells are administered, then the immune system activates immediately upon cancer cell recognition, but the activation cannot be delayed or turned off when side effects occur

Engineering Contradiction:

Improveimmune activation controlVSAvoidflexibility in marker recognition

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The CAR is divided into separate recognition polypeptides and signaling polypeptides that can be administered independently. The recognition polypeptides bind to cancer markers while the signaling polypeptides remain inactive until activated by the recognition portion, enabling controlled immune activation timing and flexibility in marker selection.

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If multiple different CARs are used to recognize multiple markers, then the therapy can target different cancer markers, but the complexity increases and cannot be adjusted post-administration

Engineering Contradiction:

Improvemarker recognition flexibilityVSAvoidnumber of different CARs

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

A single signaling polypeptide can be paired with multiple different recognition polypeptides that target different cancer markers. This universal signaling component enables one CAR construct to perform multiple functions by simply changing the recognition portion, reducing the need for multiple different CAR types.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system allows dynamic switching between different recognition polypeptides after administration by providing multiple recognition polypeptides that can bind to the same signaling polypeptide. This enables adaptability in marker recognition without requiring re-engineering of the entire CAR system.

Inventive Principle:

Principle #15Dynamics

3Ease of manufacture

If the CAR structure is simplified to a single polypeptide, then the manufacturing is easier, but the flexibility and controllability are reduced

Engineering Contradiction:

ImproveCAR production simplicityVSAvoidimmunity activation control

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS12577288B2Methods and compositions relating to chimeric antigen receptors

Publication Date: 2026.03.17 TRUSTEES OF BOSTON UNIV

AI summary

Described herein is a chimeric antigen receptor (CAR) platform with the ability to (a) serve as an ON/OFF switch (with the ability for tenability/titrability), (b) sense multiple antigens and perform logic computations, and/or (c) independently regulate multiple signaling pathways. The compositions provided herein permit the degree of control and discrimination necessary to optimize CAR T cell therapy. Also described herein are cells comprising such compositions and the use of these compositions and/or cells in the treatment of cancer.