Engineered T Cell Composition Combining CER and CAR for Solid Tumors

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Solution Overview

Problem

Treatment of solid tumors with engineered immune cells faces challenges such as trafficking to the tumor site, physical barriers, stressful metabolic landscapes, and immunosuppressive mechanisms, limiting the effectiveness of adoptive cellular immunotherapy.

Innovation Solution

Combining CD4+ T cells transduced with a chimeric engulfment receptor (CER) for phagocytic activity and CD8+ T cells transduced with chimeric antigen receptors (CAR) or T cell receptors (TCR) for cytolytic activity to enhance immune cell persistence and activity in the tumor microenvironment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If CD4+ T cells transduced with chimeric engulfment receptors (CER) are used for phagocytic activity, then tumor cell elimination through engulfment is improved, but the overall cytotoxicity and persistence of engineered immune cells is limited

Engineering Contradiction:

Improvetumor cell eliminationVSAvoidimmune cell persistence and activity

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent combines CD4+ T cells transduced with chimeric engulfment receptors (CER) and CD8+ T cells transduced with chimeric antigen receptors (CAR) or T cell receptors (TCR) into a composite cellular immunotherapy composition. This merging of different T cell subsets with distinct functional capabilities allows the treatment to simultaneously benefit from phagocytic tumor cell elimination and enhanced cytolytic activity, while the synergistic interaction between cell types improves overall persistence and effectiveness in the tumor microenvironment.

Inventive Principle:

Principle #5Merging (Combining)

2Productivity

If CD8+ T cells transduced with chimeric antigen receptors (CAR) or T cell receptors (TCR) are used for cytolytic activity, then tumor cell elimination through cytolysis is improved, but the persistence and activity of engineered immune cells in the tumor microenvironment is limited

Engineering Contradiction:

Improvetumor cell eliminationVSAvoidimmune cell persistence

Core Design Contradiction:

ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent merges CD8+ T cells with cytolytic CAR or TCR transduction with CD4+ T cells bearing CER transduction in a composite composition. The CD4+ CER+ T cells provide supportive functions including phagocytic activity and cytokine production that enhance the persistence and functional durability of the CD8+ CAR+/TCR+ cytolytic T cells within the tumor microenvironment, thereby extending the duration of effective action.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The composite immunotherapy composition achieves multi-functionality by incorporating T cell subsets that perform different functions: CD4+ CER+ T cells provide phagocytic tumor clearance and immunosuppressive counteraction, while CD8+ CAR+/TCR+ T cells provide cytolytic activity. This universal approach allows a single treatment composition to address multiple aspects of tumor elimination and immune cell persistence simultaneously.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If a combination of CER+ and CAR+/TCR+ engineered immune cells is used, then tumor cell elimination through multiple mechanisms is improved, but the complexity of the immunotherapy composition is increased

Engineering Contradiction:

Improvetumor cell eliminationVSAvoidimmunotherapy composition complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the engineered immune cell population into distinct functional subsets: CD4+ T cells transduced with CER for phagocytic activity, and CD8+ T cells transduced with CAR or TCR for cytolytic activity. This segmentation allows each subset to be optimized for its specific function while maintaining overall compositional control, facilitating standardized manufacturing and quality control procedures despite the multi-component nature of the therapy.

Inventive Principle:

Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combined approach significantly enhances the elimination of tumor cells through both cytolysis and engulfment, improving the efficacy of adoptive cell therapy by increasing cytotoxicity and persistence of engineered immune cells.

Implementation Method 1

CD4+ T cells transduced with a chimeric engulfment receptor (CER) for phagocytic activity

Methodology Applied

Scientific EffectPhagocytosis:

Implementation Method 2

CD8+ T cells transduced with chimeric antigen receptors (CAR) or T cell receptors (TCR) for cytolytic activity

Methodology Applied

Scientific EffectCytolysis:

Data Source

PatentUS20260077015A1Cellular immunotherapy compositions and uses thereof

Publication Date: 2026.03.19 CERO THERAPEUTICS HOLDINGS INC

AI summary

The present disclosure relates to cellular immunotherapy compositions comprising a combination of immune cells or cellular subsets modified with chimeric engulfment receptors and chimeric antigen receptors/or T cell receptor binding proteins, and methods of using such cellular immunotherapy compositions.