FcαR-Based Chimeric Antigen Receptor for Solid Tumor Targeting

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Solution Overview

Problem

Current CAR therapies, particularly for solid tumors, face limitations in T cell trafficking and immune resistance mechanisms, necessitating the development of new chimeric receptors to enhance immunotherapy efficacy and broaden treatment applications.

Innovation Solution

A chimeric antigen receptor (CAR) comprising an intracellular domain of the FcαR, a transmembrane domain of the FcαR, and a ligand-binding domain, specifically designed for myeloid cells and innate lymphoid cells, to amplify anti-tumor effector functions and improve tumor targeting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR therapy uses T cells with conventional signaling domains (CD3ζ, CD28, 4-1BB), then hematological malignancies show high remission rates (up to 90%), but solid tumors show limited success due to poor T cell trafficking and immune resistance

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidapplicability to solid tumors

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the intracellular signaling parameters by replacing conventional domains (CD3ζ, CD28, 4-1BB) with FcαR intracellular domain, which alters the activation threshold and signaling characteristics of the CAR-expressing cells, enabling them to overcome immune resistance in solid tumors

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite chimeric receptor structure combining extracellular antigen recognition domains with FcαR intracellular signaling domain, forming a new functional entity that integrates tumor targeting with enhanced immunomodulatory signaling capabilities

Inventive Principle:

Principle #40Composite materials

2Force

If CARs are designed with strong signaling domains to enhance tumor cell killing, then cytotoxicity increases, but off-target effects and immune resistance may worsen

Engineering Contradiction:

ImprovecytotoxicityVSAvoidoff-target effects

Core Design Contradiction:

ForceVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by confining the strong FcαR signaling activity specifically to CAR-expressing cells that have bound tumor antigens, while non-target cells expressing the same CAR do not activate this pathway without ligand binding, thus localizing the potent cytotoxic effect to the tumor microenvironment

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20240366762A1Chimeric FC-alpha receptors and uses thereof

Publication Date: 2024.11.07 SANQUIN IP BV

AI summary

The invention relates to polypeptides and chimeric antigen receptors (CARs) comprising an intracellular domain of a Fc alpha Receptor (FcαR), a transmembrane domain of a FcαR, and a ligand-binding domain, to cells comprising and expressing such polypeptides and CARs and to uses thereof.