MPC Inhibitors Enhance T-Cell Memory Phenotype for Cancer Immunotherapy

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Solution Overview

Problem

Current CAR T-cell therapies for cancer treatment face limitations in solid tumors due to poor T-cell proliferation and persistence, and existing adjuvants for vaccines do not efficiently activate both humoral and cellular immunity, necessitating improved methods to enhance T-cell memory formation and metabolic fitness.

Innovation Solution

Pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) during T-cell culture to increase the proportion of activated T cells committed to a memory phenotype, enhancing anti-tumoral activity and durability of cancer treatments, including CAR T therapy and vaccine efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If T cells with early memory phenotype are infused, then persistence and survival in vivo is improved, but current strategies dramatically inhibit T cell proliferation

Engineering Contradiction:

ImproveT cell persistenceVSAvoidT cell proliferation

Core Design Contradiction:

Duration of action of stationary objectVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying the metabolic state of T cells through MPC inhibition during ex vivo culture. This metabolic parameter change induces differentiation toward memory phenotype while maintaining proliferation capacity, resolving the contradiction between persistence and productivity.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If CAR T therapy is used for solid tumors, then anti-tumor activity is improved, but T cell proliferation and persistence remain poor

Engineering Contradiction:

Improveanti-tumor activityVSAvoidT cell persistence

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by pre-differentiating T cells toward memory phenotype during ex vivo manufacturing through MPC inhibition. This preliminary metabolic conditioning ensures that infused CAR T cells have enhanced persistence and survival capabilities before being administered to patients with solid tumors.

Inventive Principle:

Principle #10Preliminary action

3Ease of operation

If current adjuvants are used for vaccination, then antigen-presenting cell activation is improved, but efficient activation of both humoral and cellular immunity is not achieved

Engineering Contradiction:

ImproveAPC activationVSAvoiddual immunity activation

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent applies the intermediary principle by using MPC inhibition as a metabolic mediator that bridges APC activation and T cell differentiation. This intermediary metabolic intervention enables coordinated activation of both humoral and cellular immunity pathways that current adjuvants fail to achieve simultaneously.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240360143A1[1,2,4]triazolo[4,3-a]pyrimidin-7(8H)-one as mitochondrial pyruvate carrier inhibitors for use in the treatment of cancer

Publication Date: 2024.10.31 MPC THERAPEUTICS SA

AI summary

The present invention is related to compounds, methods, compositions and uses that are able to inhibit mitochondrial pyruvate carrier (MPC) activity and which are useful for immunotherapy, in particular T-cell therapies, immune check point inhibitors or anti-cancer vaccine.