Modified TCR-CD3 Complex Enhancing CAR-T Efficacy

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Solution Overview

Problem

Current CAR T cell therapy for cancer is limited by the inability to effectively target and eliminate all malignant tumors due to immune suppression and hostile tumor microenvironments, and can cause side effects in some patients.

Innovation Solution

Engineering a modified TCR-CD3 complex by linking CD3γ, ζ-chain, CD3ε, and/or CD3δ to co-stimulatory signaling domains to enhance T cell activation and effector functions, thereby overcoming immune suppression and improving therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR T cell therapy is used to treat cancer, then some malignant tumors can be targeted and eliminated, but the therapy is limited by immune suppression and hostile tumor microenvironments that prevent effective targeting of all malignant tumors

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidimmune suppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines multiple signaling domains (CD3γ, ζ-chain, CD3ε, CD3δ) into a single modified TCR-CD3 complex to integrate multiple activation signals, thereby overcoming immune suppression and enhancing therapeutic efficacy against malignant tumors

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The modified TCR-CD3 complex uses composite signaling architecture by linking multiple CD3 chain components together, creating a enhanced signaling molecule that overcomes the limitations of conventional single-chain CAR T cell therapy

Inventive Principle:

Principle #40Composite materials

2Productivity

If conventional CAR T cell therapy is used to treat cancer, then some cancer cells can be eliminated, but side effects occur in some patients

Engineering Contradiction:

Improveanti-tumor responseVSAvoidside effects

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies specific local regions of the TCR-CD3 complex by linking particular CD3 chains (γ, ζ, ε, δ) with co-stimulatory domains, creating localized enhancements in signaling capability that improve anti-tumor response while maintaining selective targeting to reduce off-target side effects

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11858977B2Modified TCR and uses thereof

Publication Date: 2024.01.02 INNOVATIVE CELLULAR THERAPEUTICS HLDG LTD

AI summary

Embodiments relate to a modified cell engineered to comprise a modified TCR-CD3 complex, wherein the CD3γ, ζ-chain, CD3ε, and/or CD3δ chains of the modified TCR-CD3 complex are linked to one or more co-stimulatory signaling domains.