HHLA2 Fusion Protein Modulates T Cell Activity

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Solution Overview

Problem

Current therapies lack effective solutions for autoimmune diseases, transplant rejection, and cancer treatment, particularly in regulating T cell responses and immune evasion mechanisms.

Innovation Solution

The development of an HHLA2-immunoglobulin-fusion protein and anti-HHLA2 antibody or fragments to modulate T cell activity, targeting the HHLA2 pathway to treat autoimmune diseases, suppress transplant rejection, and combat cancer by inhibiting T cell proliferation and cytokine production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used for autoimmune diseases and transplant rejection, then treatment options are limited, but therapeutic effectiveness is insufficient

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment options

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces HHLA2 as a novel coinhibitory molecule that acts as an intermediary in immune regulation. HHLA2 binds to PD-1 on T cells to deliver coinhibitory signals, serving as a mediator between antigen-presenting cells and T cells. This new intermediary pathway provides enhanced therapeutic effectiveness for autoimmune diseases and transplant rejection by adding a new mechanism of immune suppression that complements existing therapies.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If HHLA2 pathway is targeted to suppress T cell responses, then autoimmune diseases and transplant rejection are treated, but cancer treatment efficacy may be reduced

Engineering Contradiction:

Improveeffectiveness for autoimmune diseases and transplant rejectionVSAvoidcancer progression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by directing HHLA2-based therapy to specific contexts. HHLA2 is strategically expressed on antigen-presenting cells in autoimmune and transplant contexts to suppress pathogenic T cell responses. In cancer, the therapy is designed to selectively block HHLA2-PD-1 interactions in the tumor microenvironment while preserving systemic immune regulation, thereby treating autoimmune diseases and transplant rejection without compromising anti-tumor immunity.

Inventive Principle:

Principle #3Local quality

3Reliability

If HHLA2 is used as a coinhibitory molecule, then T cell activation is suppressed, but immune evasion by cancer cells may be enhanced

Engineering Contradiction:

ImproveT cell activation suppressionVSAvoidimmune evasion

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies inversion by reversing the typical immune evasion strategy. Instead of allowing HHLA2 to be upregulated by cancer cells for immune evasion (the conventional approach), the invention uses HHLA2 as a therapeutic agent delivered by antigen-presenting cells. This inverted approach transforms HHLA2 from a potential evasion mechanism into a controlled therapeutic tool that suppresses pathogenic T cell responses in autoimmune and transplant contexts while maintaining anti-tumor immunity through selective blockade of the HHLA2-PD-1 pathway.

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS11261253B2HHLA2 as a novel inhibitor of human immune system and uses thereof

Publication Date: 2022.03.01 ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV

AI summary

Provided are methods of treating an autoimmune disease in a subject, or of suppressing transplant rejection in a subject, or of treating a cancer in a subject, as well as compositions therefor.