T-Cell-MP-Epitope Conjugates for Targeted Cancer Immunotherapy

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Solution Overview

Problem

Current cancer therapies lack effective targets for inducing adaptive immune responses against MAGE and NY-ESO proteins, which are aberrantly expressed in various cancers, limiting the specificity and efficacy of immunotherapies.

Innovation Solution

Development of T-Cell-MP-MAGE-epitope conjugates and T-Cell-MP-NY-ESO-epitope conjugates, which engage T cells by providing both the epitope-specific signal through MHC-epitope-TCR interaction and costimulatory signals, driving adaptive immune responses against cancer cells expressing these proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cancer therapies are used, then treatment can be provided, but the specificity and efficacy of immunotherapies are limited due to lack of effective targets

Engineering Contradiction:

Improveefficacy of immunotherapyVSAvoidspecificity of immune response

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention segments the T cell activation process into two distinct signals: (1) epitope-specific signal through MHC-epitope-TCR interaction, and (2) costimulatory signal through MOD-CoMOD interaction. This segmentation allows independent optimization of specificity (via epitope binding) and efficacy (via costimulation), resolving the contradiction between these two parameters in cancer therapy

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The T-Cell-MP molecule acts as an intermediary that bridges the gap between epitope presentation and T cell activation. It combines the MHC-epitope complex (providing specificity) with costimulatory molecules (providing efficacy) in a single therapeutic agent, enabling both specific and effective immune response against cancer cells expressing MAGE or NY-ESO proteins

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If T cell activation is achieved through epitope presentation alone, then specificity is maintained, but costimulatory signals are insufficient for effective adaptive immune response

Engineering Contradiction:

Improveefficacy of T cell activationVSAvoidcomplexity of activation signals

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention merges epitope presentation (MHC-epitope complex) and costimulatory signals (MOD molecules) into a single integrated T-Cell-MP construct. This combination provides both specificity (through epitope recognition) and efficacy (through costimulation) in one molecule, achieving reliable T cell activation without requiring multiple separate agents or complex signal delivery systems

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20250041396A1T Cell Modulatory Polypeptides with Conjugation Sites and Methods of Use Thereof

Publication Date: 2025.02.06 CUE BIOPHARMA INC

AI summary

The present disclosure provides T cell modulatory polypeptide-epitope conjugates (T-Cell-MP-epitope conjugates) comprising a chemical conjugation site at which an NY-ESO (e.g., NY-ESO-1 or NY-ESO-2) or a MAGE (e.g., MAGEA4) peptide epitope is covalently attached and at least one immunomodulatory polypeptide sequence that may be variant selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-MP-epitope conjugates are useful for modulating the activity (e.g., increasing proliferation or cytotoxic activity) of T-cells specific to the NY-ESO or MAGE peptide epitope in an epitope selective/specific manner, and accordingly, for treating individuals with, for example, cancers expressing the covalently attached epitope. The disclosure also provides T-Cell-MP-epitope conjugates with targeting sequences that can server to, among other things, localize the T-Cell-MP-epitope conjugates to a specific tissue or cell type.