HBV Surface Antigen TCR Engineering for Safer HCC Cell Targeting

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Solution Overview

Problem

Current treatments for HBV-related HCC are inadequate, with existing immunotherapies showing limited efficacy and safety concerns, and there is a need for novel therapeutic strategies to target HBV surface antigens effectively.

Innovation Solution

Development of T cell receptors (TCRs) that specifically bind to the hepatitis B surface antigen, particularly the FLLTRILTI-HLA-A2 complex, to eliminate liver cancer cells caused by HBV infection, utilizing genetically engineered TCR-T cells with optimized CDR sequences and enhanced stability through disulfide bonds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing immunotherapies are used to treat HBV-related HCC, then treatment coverage is provided, but efficacy is limited and safety concerns arise

Engineering Contradiction:

Improvetreatment efficacyVSAvoidsafety concerns

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the TCR structure by optimizing CDR sequences and introducing disulfide bonds to enhance stability and affinity. This changes the molecular parameters of the TCR to improve its ability to recognize HBV surface antigens while maintaining safety, directly addressing the limited efficacy of existing immunotherapies without compromising patient safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite TCR structure combining optimized CDR regions with stable framework regions and engineered disulfide bonds. This composite design integrates multiple functional elements (antigen recognition, structural stability, affinity) into a single therapeutic agent that overcomes the limitations of existing immunotherapies

Inventive Principle:

Principle #40Composite materials

2Reliability

If TCR sequences are optimized for higher affinity binding, then anti-viral ability is enhanced, but structural stability may be compromised

Engineering Contradiction:

Improveanti-viral abilityVSAvoidstructural stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent simultaneously optimizes multiple parameters: CDR sequences are modified to increase antigen-binding affinity while disulfide bonds are introduced to enhance structural stability. This multi-parameter optimization resolves the trade-off between affinity and stability, achieving both enhanced anti-viral ability and structural integrity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent preemptively introduces disulfide bonds into the TCR structure to provide structural cushioning and stability. This prior reinforcement prevents potential structural compromise that might result from optimizing CDR sequences for higher affinity, ensuring both high anti-viral ability and structural stability

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentUS20260021140A1HBV Surface Antigen Specific T Cell Receptors And Uses Thereof

Publication Date: 2026.01.22 SCG CELL THERAPY PTE LTD

AI summary

Provided are HLA-A02 restricted T cell receptors (TCRs) that specifically target HBV surface antigen which is a S20 peptide consisting of FLLTRILTI and the T cells expressing said TCRs. It also relates to the nucleic acid molecules and vectors encoding said TCRs and their medical uses in reducing HBV antigen-positive tumour cells and treating or preventing HBV infections and related diseases.