Cyclin A1-Specific TCR Engineering for Targeted Tumor Cell Killing

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Solution Overview

Problem

Current adoptive immunotherapy methods for treating cancers with cyclin A1 overexpression, such as acute myeloid leukemia, lack effective tumor-reactive T cells that specifically target cyclin A1, limiting therapeutic efficacy.

Innovation Solution

Development of cyclin A1-specific T cell receptors (TCRs) that bind to cyclin A1 peptides presented by MHC molecules, enabling the generation of tumor-reactive T cells for targeted cancer treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional adoptive immunotherapy methods are used, then treatment can be provided to patients, but the therapy lacks effective tumor-reactive T cells that specifically target cyclin A1, limiting therapeutic efficacy

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidspecificity to cyclin A1

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces T cell receptors with specifically engineered binding regions (CDR3 domains) that are locally optimized to recognize cyclin A1 peptides presented by HLA-A2 molecules. This local specialization of the TCR binding interface enables high-specificity targeting of cyclin A1-expressing tumor cells while maintaining the general framework of adoptive immunotherapy

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent systematically varies key parameters of the TCR structure, particularly the complementary determining regions (CDR1, CDR2, CDR3) of the alpha and beta chains, to optimize binding affinity and specificity for cyclin A1 peptide-HLA-A2 complexes. Multiple TCR variants with different amino acid sequences are generated and screened to identify those with enhanced therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The cyclin A1-specific TCRs enhance the therapeutic potential of adoptive immunotherapy by specifically targeting and killing cyclin A1-overexpressing cancer cells, providing a targeted and effective treatment approach.

Implementation Method 1

T cell receptors (TCRs) that specifically recognize and bind to cyclin A1 peptides presented by major histocompatibility complex (MHC) molecules

Methodology Applied

Scientific EffectAntigen recognition:

Implementation Method 2

methods for generating tumor-reactive T cells for targeted cancer treatment

Methodology Applied

Scientific EffectT cell-mediated cytotoxicity:

Data Source

PatentUS12570712B2Cyclin A1 specific T cell receptors and uses thereof

Publication Date: 2026.03.10 FRED HUTCHINSON CANCER CENT

AI summary

The present disclosure provides binding proteins, including TCRs, that specifically bind human cyclin A1 (CCNA1), host cells expressing such antigen specific binding proteins, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress CCNA1, such as in cancer.