Dual CAR T Cells for Solid Tumor Expansion and Maintenance

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Solution Overview

Problem

Current CAR T cell therapy is effective for treating blood cancers but struggles to achieve long-term maintenance and efficacy for solid tumors, necessitating improved methods to expand and maintain CAR T cells in patients.

Innovation Solution

The use of genetically modified cells expressing multiple antigen binding domains, including a first domain for expanding and maintaining CAR T cells and a second domain for targeting and killing tumor cells, enhances the therapeutic efficacy of CAR T cell therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR T cells are used to treat solid tumors, then tumor targeting capability is improved, but long-term maintenance and persistence of CAR T cells deteriorates

Engineering Contradiction:

Improvetumor targeting capabilityVSAvoidlong-term maintenance of CAR T cells

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent divides the CAR T cell population into two distinct subsets: (1) CAR T cells expressing a first antigen binding domain specific to solid tumor antigens for tumor targeting, and (2) CAR T cells expressing a second antigen binding domain specific to B cell markers for expansion and maintenance. This segmentation allows each subset to perform its specialized function optimally without compromise

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses B cells as an intermediary host to support the expansion and maintenance of CAR T cells. The second antigen binding domain targets B cell surface markers, allowing CAR T cells to utilize B cells as a biological niche for persistence and expansion in the patient's body, thereby solving the long-term maintenance problem

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If CAR T cells are expanded in the patient using B cells, then quantity of CAR T cells is improved, but complexity of the therapeutic approach deteriorates

Engineering Contradiction:

Improvequantity of CAR T cellsVSAvoidcomplexity of therapeutic approach

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent creates a dual-function CAR T cell therapy where the same modified T cells can both target tumors directly (via first antigen binding domain) and expand through B cell interaction (via second antigen binding domain). This multi-functionality reduces the need for separate expansion protocols and simplifies the overall therapeutic approach

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent enables CAR T cells to self-expand within the patient's body by utilizing the second antigen binding domain to interact with abundant B cells. This self-service expansion mechanism eliminates the need for external expansion facilities, repeated infusions, or complex ex vivo manipulation, thereby reducing therapeutic complexity

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS20250188146A1Modified Cell Expansion and Uses Thereof

Publication Date: 2025.06.12 INNOVATIVE CELLULAR THERAPEUTICS INC

AI summary

The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion and/or maintenance in vivo and/or in vitro. For example, a method of enhancing T cell-based therapy comprises administering genetically modified T cells comprising a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR binds a surface molecule or antigen of a white blood cell.