Engineered T Cell Receptor for Directed NKT Cell Differentiation

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Solution Overview

Problem

Natural killer T (NKT) cells have a short half-life in the body, lack specific antibodies, and are insufficiently enriched around tumors, limiting their effectiveness in cell therapy, and their scarcity in peripheral blood makes them difficult to use.

Innovation Solution

A T cell receptor (TCR) with specific CDR3 sequences is engineered to enhance the proliferation, killing ability, and directed differentiation of cells, including fusion proteins and vectors for expression in stem cells to produce NKT cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If NKT cells are used for cell therapy, then immune response is activated, but their short half-life and lack of specific antibodies limit their effectiveness

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidhalf-life of NKT cells

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent uses TCR as an intermediary component that can be transduced into stem cells to enable them to differentiate into NKT cells with enhanced functionality. The TCR acts as a mediator that bridges the gap between stem cells and functional NKT cells, providing both the differentiation guidance and the antigen recognition capability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the genetic parameters of stem cells by transducing them with specific TCR sequences. This genetic modification alters the differentiation parameters of stem cells, directing them to become NKT cells with improved half-life and enhanced therapeutic capabilities including specific antibody production.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If NKT cells are infused for treatment, then immune response is enhanced, but repeated infusions are required due to short half-life

Engineering Contradiction:

Improveimmune response efficacyVSAvoidtime for repeated infusions

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary action by transducing stem cells with TCR sequences before differentiation. This pre-modification ensures that when the cells differentiate into NKT cells, they already possess the enhanced functionality and extended half-life characteristics, eliminating the need for repeated infusions.

Inventive Principle:

Principle #10Preliminary action

3Productivity

If TCR is transduced into stem cells, then directed differentiation to NKT is improved, but the complexity of the treatment protocol increases

Engineering Contradiction:

Improvedifferentiation efficiencyVSAvoidtreatment protocol complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts only the essential TCR sequences needed for NKT cell differentiation and transduces them into stem cells. This extraction approach simplifies the treatment protocol by focusing on the critical genetic element (TCR) rather than requiring complex combinations of multiple factors or procedures.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentEP4703375A1T cell receptor and use thereof

Publication Date: 2026.03.04 BEIJING GRIT BIOTHERAPEUTICS CO LTD

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AI summary

The present invention relates to the field of biomedicines and particularly provides a T cell receptor (TCR) and use thereof. The TCR can be used for modifying cells in order to improve or promote the expression of the proliferation capability, killing capability, and/or directed differentiation capability of the TCR cell.