PD-1 Antibody-Secreting CAR-T Cells for Solid Tumor Immunosuppression

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Solution Overview

Problem

CAR-T therapy is limited by life-threatening toxicities, limited efficacy against solid tumors due to the immunosuppressive tumor microenvironment, physical tumor barriers, and the development of tumor resistance and antigen escape.

Innovation Solution

Development of a recombinant PD-1 antibody and a chimeric antigen receptor (CAR) expressed on immune cells, such as T cells, to enhance tumor penetration, overcome immunosuppression, and improve anti-tumor response by blocking the PD-1/PD-L1 pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR-T therapy is used to treat solid tumors, then anti-tumor response is enhanced, but the immunosuppressive tumor microenvironment limits penetration and infiltration of CAR-T cells

Engineering Contradiction:

Improveanti-tumor responseVSAvoidimmunosuppressive tumor microenvironment

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a secreted PD-1 antibody as an intermediary substance that blocks the PD-1/PD-L1 interaction in the tumor microenvironment. This antibody acts as a mediator to counteract the immunosuppressive signals, enabling CAR-T cells to maintain their anti-tumor activity and penetrate the tumor microenvironment more effectively.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs preliminary anti-action by pre-treating or concurrently administering a PD-1 antibody to block the immunosuppressive PD-1 pathway before CAR-T cells encounter the tumor microenvironment. This preemptive blocking prevents the tumor microenvironment from suppressing CAR-T cell function, thereby maintaining their efficacy against solid tumors.

Inventive Principle:

Principle #9Preliminary anti-action

2Reliability

If CAR-T cells are engineered to recognize target antigens, then tumor cell elimination is improved, but tumor resistance and antigen escape develop

Engineering Contradiction:

Improvetumor cell eliminationVSAvoidtumor resistance

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent implements continuity of useful action through the secreted PD-1 antibody that continuously blocks the PD-1/PD-L1 pathway in the tumor microenvironment. This continuous blocking prevents tumor cells from exploiting the PD-1 pathway to evade immune detection, thereby maintaining sustained anti-tumor activity and reducing the development of resistance.

Inventive Principle:

Principle #20Continuity of useful action

3Reliability

If CAR-T therapy is administered, then treatment efficacy is improved, but life-threatening toxicities occur

Engineering Contradiction:

Improvetreatment efficacyVSAvoidlife-threatening toxicities

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful immunosuppressive PD-1 pathway into a beneficial target by using a PD-1 antibody to block it. By targeting the PD-1 pathway that tumors exploit for immune evasion, the therapy enhances anti-tumor efficacy while the controlled approach of using a humanized antibody minimizes off-target toxicities.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20250381225A1Recombinant antibodies, chimeric antigen receptors, and uses thereof in treating cancers

Publication Date: 2025.12.18 DEV CENT FOR BIOTECHNOLOGY

AI summary

Disclosed herein are recombinant antibodies specific to programmed death 1 (PD-1), chimeric antigen receptors (CARs) and genetically modified cells configured to express the CARs on their surfaces and secret the recombinant antibodies specific to PD-1. Also disclosed herein is a method of treating cancer by administering the genetically modified cells to a subject afflicted with cancer.