HLA-G Targeted CAR T-Cell Therapy for Solid Tumors

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current cancer immunotherapy approaches, such as CAR T-cell therapy, face challenges in targeting solid tumors effectively due to off-target expression of antigens in normal tissues, limiting their efficacy and specificity.

Innovation Solution

Development of novel anti-HLA-G antibodies and chimeric antigen receptors (CARs) specific to HLA-G, which include an antigen binding domain, a hinge domain, a transmembrane domain, and signaling domains, to selectively target and inhibit tumor cells while minimizing damage to normal tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR T-cell therapy targets are used, then immune response is activated, but off-target expression in normal tissues causes harmful effects

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidoff-target damage to normal tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the immune response by using HLA-G specific CARs that distinguish between tumor-expressing HLA-G and normal tissues. The CAR T-cells are segmented to target only HLA-G positive cells, leaving HLA-G negative normal tissues unaffected, thus resolving the off-target toxicity issue while maintaining therapeutic efficacy

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

HLA-G serves as an intermediary marker that is selectively expressed on tumor cells but not on most normal tissues. The CAR T-cells use HLA-G as an intermediary target to mediate selective tumor killing, avoiding direct attack on normal tissues and thereby reducing off-target harmful effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If broad antigen targeting is used, then tumor coverage is increased, but specificity decreases leading to reduced therapeutic index

Engineering Contradiction:

Improvetumor targeting coverageVSAvoidtargeting specificity

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by creating CAR T-cells with specialized HLA-G specificity tailored for solid tumors. The CAR design incorporates local adaptations in the antigen binding domain to recognize HLA-G variants expressed on different tumor types, providing both broad coverage and high specificity simultaneously

Inventive Principle:

Principle #3Local quality

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 anti-HLA-G antibodies and CARs demonstrate high specificity and affinity for HLA-G, potentially enhancing the therapeutic index of cancer immunotherapy by selectively targeting cancer cells, thereby improving treatment outcomes with reduced side effects.

Implementation Method 1

an isolated antibody comprising a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the antibody binds to an epitope of human HLA-G

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

chimeric antigen receptors (CARs) specific to HLA-G, which include an antigen binding domain, a hinge domain, a transmembrane domain, and signaling domains

Methodology Applied

Scientific EffectSignal transduction:

Data Source

PatentUS20240392011A1HLA-g as a novel target for car t-cell immunotherapy

Publication Date: 2024.11.28 UNIV OF SOUTHERN CALIFORNIA

AI summary

CAR cells targeting and antibodies human HLA-G are described as a new method of cancer treatment. It is proposed that HLA-G CAR cells are safe and effective in patients and can be used to treat human tumors expressing the HLA-G.