MLL Phosphopeptide-Binding TCRs for Specific Cancer Cell Targeting

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Solution Overview

Problem

There is a need for novel compositions that can recognize cancer cells presenting MLL phosphopeptides on their surface and direct an immune response against these cells, as existing technologies lack effective T cell receptors (TCRs) capable of targeting MLL phosphopeptides for cancer immunotherapy.

Innovation Solution

Development of T cell receptors (TCRs) that specifically bind to MLL phosphopeptides, such as MLL-pM EPR[pS]PSHSM and MLL-pP RVR[pS]PTRSP, with defined complementarity determining regions (CDRs) to direct an immune response against cancer cells expressing these phosphopeptides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing TCR technologies are used, then general T cell function is maintained, but specific recognition and binding to MLL phosphopeptides is insufficient for effective cancer immunotherapy

Engineering Contradiction:

Improvespecific recognition and binding to MLL phosphopeptidesVSAvoidability to target multiple cancer cell variants

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The TCR is divided into alpha and beta chains with further segmentation into variable regions (Vα, Vβ) and complementarity determining regions (CDR1α/β, CDR2α/β, CDR3α/β). This segmentation allows independent optimization of each region's binding properties to MLL phosphopeptides while maintaining overall TCR functionality.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by specifically engineering the CDR3α and CDR3β regions with particular amino acid sequences that provide high-affinity binding to MLL phosphopeptides, while other regions maintain more general TCR structural properties. This localized optimization enables specific phosphopeptide recognition without compromising overall T cell function.

Inventive Principle:

Principle #3Local quality

2Reliability

If TCRs are engineered with high specificity for MLL phosphopeptides, then cancer cell targeting capability is improved, but complexity of TCR structure and production increases

Engineering Contradiction:

Improvecancer cell targeting capabilityVSAvoidTCR structure and production complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by pre-defining optimal amino acid sequences for the CDR regions based on phosphopeptide binding requirements. These pre-engineered sequences are then directly incorporated into the TCR construct, eliminating the need for complex iterative optimization during production and simplifying the overall development process.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by modifying specific amino acid parameters in the CDR regions (particularly CDR3α and CDR3β) to achieve high-affinity binding to MLL phosphopeptides. These targeted parameter modifications in specific regions allow high specificity without requiring complex changes throughout the entire TCR structure.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP3679062B1T cell receptors that bind to mixed lineage leukemia (MLL)-specific phosphopeptides and methods of use thereof

Publication Date: 2025.11.19 MINK THERAPEUTICS INC

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AI summary

Provided are TCRs (e.g., TCRs that bind to MLL, e.g., TCRs that bind to an MLL phosphopeptide, e.g., TCRs that bind to an MLL phosphopeptide/MHC complex), cells and pharmaceutical compositions comprising these TCRs, nucleic acids encoding these TCRs, expression vectors and host cells for making these TCRs, and methods of treating a subject using these TCRs.