Genetically Modified CAR-T Cells for Tumor Infiltration

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Solution Overview

Problem

Current CAR-T cell therapy faces challenges in overcoming tumor immune suppression and metabolic hostile tumor microenvironments, limiting its effectiveness in cancer treatment.

Innovation Solution

Modification of T cells, dendritic cells, NK cells, or macrophages with enhanced or reduced expression of specific genes such as CXCR3, SLC1A3, YAP, TIGIT, S1P1, and IL-35, equipped with chimeric antigen receptors (CAR) or T Cell Receptors (TCR), to enhance their antigen binding capabilities and infiltration into tumor microenvironments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If T cells are genetically engineered with CAR to target malignancies, then anti-tumor efficacy is improved, but tumor immune suppression and metabolic hostile microenvironment limit effectiveness

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidtumor immune suppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by genetically modifying T cells to alter their metabolic parameters and gene expression profiles. Specifically, the engineered T cells have modified metabolic pathways that allow them to withstand the hostile tumor microenvironment, changing their physiological parameters to overcome immune suppression and improve anti-tumor efficacy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite cellular structures by combining CAR-T cell engineering with additional genetic modifications. The T cells are engineered with multiple components including CAR receptors, metabolic modification genes, and regulatory elements, creating a composite cellular system that can function effectively in the tumor microenvironment

Inventive Principle:

Principle #40Composite materials

2Strength

If T cells are re-engineered to attack cancer, then cytotoxic function is enhanced, but metabolic hostile tumor microenvironment reduces cell survival

Engineering Contradiction:

Improvecytotoxic functionVSAvoidcell survival in tumor microenvironment

Core Design Contradiction:

StrengthVSDuration of action of stationary object

Solution Approach 1:

The patent changes metabolic parameters of T cells through genetic engineering. The modified T cells have altered glucose metabolism, amino acid metabolism, and other metabolic pathways that enable them to survive and maintain cytotoxic function in the metabolically hostile tumor microenvironment, thereby extending their duration of action

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The genetically engineered T cells possess self-service capabilities through autonomous metabolic adjustments. The cells can independently adapt their metabolism to the tumor microenvironment conditions, generating their own survival mechanisms without external support, which maintains their cytotoxic function over extended periods

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS11701385B2Modulation of cell function for immunotherapy

Publication Date: 2023.07.18 INNOVATIVE CELLULAR THERAPEUTICS HLDG LTD

AI summary

Embodiments relate to a modified cell comprising an antigen binding molecule, and the expression and/or function of one or more genes in the modified cell has been enhanced or reduced or eliminated. The one or more genes include CXCR3, SLC1A3, YAP, TIGIT, S1P1, and IL-35. In embodiments, the cell is a T cell, a dendritic cell, a NK cell, or a macrophage cell. In embodiments, the antigen binding molecule comprises a chimeric antigen receptor (CAR) and/or the second antigen binding molecule is a T Cell Receptor (TCR).