CAR-T and PD-1 Inhibitor Combination Therapy for Tumor Progression

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Solution Overview

Problem

Current cancer treatments, particularly for B cell malignancies, face challenges in achieving clinical effectiveness due to the poor immunogenicity of tumor antigens and mechanisms tumors use to evade immune attacks, and CAR-T cell therapies struggle with persistence and efficacy over time.

Innovation Solution

A combination therapy using chimeric antigen receptor (CAR) expressing immune effector cells that target CD19 antigens in conjunction with PD-1 inhibitors to enhance immune cell activation, expansion, and persistence, thereby improving therapeutic outcomes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If CAR-T cell therapy is used to target tumor antigens, then immune attack capability is improved, but T cell persistence and proliferation capacity deteriorate due to exhaustion and suppression

Engineering Contradiction:

Improveimmune attack capabilityVSAvoidT cell persistence

Core Design Contradiction:

StrengthVSDuration of action of moving object

Solution Approach 1:

The patent introduces PD-1 inhibitors as intermediary substances that block the interaction between PD-1 and its ligands (PD-L1/PD-L2). This mediator prevents the suppressive signaling pathway that would otherwise inhibit T cell function, thereby maintaining T cell persistence and proliferation capacity while preserving the immune attack capability against tumor antigens.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If CAR-T cells are engineered to recognize tumor antigens, then tumor targeting capability is improved, but T cell function deteriorates due to anergy and exhaustion from continuous antigen exposure

Engineering Contradiction:

Improvetumor targeting capabilityVSAvoidT cell function

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent converts the harmful effect of continuous antigen exposure (which causes T cell exhaustion) into a beneficial outcome by simultaneously administering PD-1 inhibitors. The PD-1 blockade transforms the exhausted T cell state back into an activated state, allowing the highly specific tumor-targeting CAR-T cells to maintain their function over time. The very mechanism that causes exhaustion (continuous antigen recognition) becomes the basis for sustained efficacy when combined with PD-1 inhibition.

Inventive Principle:

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

3Productivity

If traditional cancer therapies are used to treat B cell malignancies, then tumor cells are killed, but serious side effects and poor clinical effectiveness occur due to poor immunogenicity of tumor antigens

Engineering Contradiction:

Improvetumor cell killing efficiencyVSAvoidserious side effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces traditional mechanical/chemical cancer therapies (chemotherapy, radiation) with a biological immune-based system. Instead of using non-specific cytotoxic agents that damage both tumor and normal cells, the invention uses genetically modified T cells that specifically recognize and kill tumor cells expressing target antigens like CD19, thereby achieving high tumor cell killing efficiency with reduced harmful side effects.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentEP3491016A1Combination therapies of chimeric antigen receptors and PD-1 inhibitors

Publication Date: 2019.06.05 NOVARTIS AG

AI summary

Provided are compositions and methods for treating diseases, e.g., cancers, e.g., diseases associated with expression of an antigen, e.g., CD 19, comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to the antigen, e.g., CD19, in combination with a PD-1 inhibitor.