CAR T-Cell Costimulatory Co-Expression for Enhanced Antigen Presentation

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Solution Overview

Problem

Existing CAR-based therapies for adoptive transfer of cytotoxic T lymphocytes (CTLs) are less than optimal in terms of effectiveness, safety, and efficiency, necessitating improvements for enhanced anti-tumor activity.

Innovation Solution

Engineering T cells to co-express a chimeric antigen receptor (CAR) and one or more enhancers of T cell priming (ETPs), which confer enhanced professional antigen-presenting cell function, providing transient yet prolonged immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR-based T cell therapy is used, then antigen-specific cytotoxicity is achieved, but anti-tumor effectiveness is insufficient

Engineering Contradiction:

Improveanti-tumor effectivenessVSAvoidanti-tumor activity

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent combines CAR T cells with antigen-presenting cell functions by co-introducing costimulatory molecules (CD80, CD86, CD40) and MHC molecules into the T cells. This merging of cytotoxic T cell capabilities with APC functions creates a dual-functional cell that can both directly kill tumor cells and present antigens to activate additional T cells, thereby enhancing overall anti-tumor effectiveness

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The engineered T cells acquire multiple functions: (1) antigen recognition via CAR, (2) direct cytotoxicity through T cell receptor-mediated killing, (3) antigen presentation via MHC molecules, and (4) costimulation via CD80/CD86/CD40 molecules. This multi-functionality allows a single cell type to perform roles previously requiring multiple different cell types

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If CAR T cells are engineered with costimulatory molecules, then antigen presentation ability is enhanced, but cell complexity increases

Engineering Contradiction:

Improveantigen presentation abilityVSAvoidcell engineering complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Multiple functional components (CAR, costimulatory molecules, MHC molecules) are combined into a single T cell through co-introduction of multiple nucleic acid sequences. This consolidation of multiple gene delivery events into one engineering process, while increasing functional complexity, streamlines the overall cell preparation workflow

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The T cell is engineered to express a composite set of molecules including the CAR complex (scFv-transmembrane-signaling domains), costimulatory molecules (CD80, CD86, or CD40), and MHC class I or class II molecules. This composite molecular profile creates a cell with enhanced and multifaceted anti-tumor capabilities

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20250296977A1Enhanced antigen presenting ability of car t cells by co-introduction of costimulatory molecules

Publication Date: 2025.09.25 NOVARTIS AG

AI summary

The invention provides T cells comprising nucleic acid sequence encoding a chimeric antigen receptor and a nucleic acid sequence encoding an enhancer of T cell priming, compositions including the T cells, and methods of using the T cells to treat diseases associated with the expression of disease-associated antigens.