PD-1 Chimeric Receptor Immune Cell Therapy for Solid Tumors

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Solution Overview

Problem

Current checkpoint inhibitor therapies for cancer, such as those targeting PD-1 and PD-L1, face limitations in efficacy due to cancer cell heterogeneity, immunosuppressive tumor microenvironments, and inefficient tumor penetration by immune cells.

Innovation Solution

Development of immune cell therapies expressing a chimeric receptor comprising the extracellular domain of PD-1, a transmembrane domain, and a costimulatory domain, which enables enhanced penetration and activation of tumor-specific cytotoxic T cells, and modulation of the immunosuppressive tumor microenvironment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional immune cell therapies are used, then immune system function is restored to some extent, but tumor penetration efficiency remains insufficient

Engineering Contradiction:

Improvetumor penetration efficiencyVSAvoidtherapeutic efficacy

Core Design Contradiction:

SpeedVSReliability

Solution Approach 1:

The patent modifies the immune cell receptor parameters by creating a chimeric receptor that combines PD-1 extracellular domain with CD3ζ intracellular signaling domain and costimulatory domains. This parameter change in receptor structure enables the immune cells to effectively recognize PD-L1 on tumor cells while receiving appropriate activation signals, thereby improving both penetration efficiency and therapeutic efficacy simultaneously

Inventive Principle:

Principle #35Parameter changes

2Reliability

If checkpoint inhibitors targeting PD-1/PD-L1 are administered, then immune response is restored, but the immunosuppressive tumor microenvironment remains challenging to overcome

Engineering Contradiction:

Improveimmune response restorationVSAvoidimmunosuppressive tumor microenvironment

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses engineered immune cells expressing chimeric PD-1 receptors as intermediaries that can penetrate the immunosuppressive tumor microenvironment. These cells serve as mediators between the immune system and tumor cells, capable of navigating through the suppressive environment while maintaining their cytotoxic function against PD-L1 positive tumor cells

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If immune cell therapy is applied, then T cell activity against tumor is enhanced, but heterogeneity among cancer cells limits overall efficacy

Engineering Contradiction:

ImproveT cell activationVSAvoidcancer cell heterogeneity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal immune cell therapy platform using chimeric PD-1 receptors that can recognize PD-L1 across different cancer types and heterogeneous tumor cell populations. The costimulatory domains incorporated into the receptor provide multi-functional signaling capabilities that enable consistent T cell activation regardless of the specific cancer cell heterogeneity, making the therapy broadly applicable

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250009880A1Immune cell therapy of PD-l1 positive cancers

Publication Date: 2025.01.09 VITA THERAPEUTICS INC

AI summary

The present disclosure provides new anti-cancer immune cells engineered to express chimeric receptors which, unlike the conventional chimeric antigen receptors (CAR), employ the extracellular domain of PD-1 that is capable of binding PD-L1 that is expressed on a target tumor cell. The immune cell is preferably an immature myeloid cell that is p50 deficient. Such an engineered immune cell exhibits improved therapeutic efficacy as compared to the conventional immune cell therapies and is more broadly applicable to different types of cancers expressing, or induced to express PD-L1.