Anti-NKG2A Antibody Blocking HLA-E Immune Evasion

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Solution Overview

Problem

Tumor cells evade immune recognition by expressing high levels of HLA-E and NKG2A, inhibiting the killing activity of NK and CD8+ T cells, allowing them to escape immune clearance.

Innovation Solution

Development of an anti-NKG2A antibody that specifically binds to NKG2A on human NK cells, blocking the NKG2A and HLA-E signaling pathways to enhance the killing activity of NK cells on HLA-E positive tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If tumor cells express high levels of HLA-E and NKG2A, then immune evasion is enhanced, but killing activity of NK and CD8+ T cells is inhibited

Engineering Contradiction:

Improveimmune evasion capabilityVSAvoidkilling activity of NK and CD8+ T cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful immune evasion mechanism into a beneficial therapeutic target. By developing an antibody that specifically binds to NKG2A on tumor cells, the invention transforms the tumor's immune evasion capability (high NKG2A expression) into a vulnerability that can be exploited for immunotherapy, thereby enhancing NK cell-mediated killing of tumor cells

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The anti-NKG2A antibody serves as an intermediary molecule that bridges NK cells and tumor cells. The antibody binds to NKG2A on tumor cells and simultaneously engages with NK cells, facilitating enhanced killing activity. This intermediary mechanism overcomes the inhibitory signaling that normally prevents NK cell activation

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If NKG2A and HLA-E signaling pathways are blocked, then killing activity of NK cells is enhanced, but tumor cell survival is compromised

Engineering Contradiction:

Improvekilling activity of NK cellsVSAvoidtumor cell survival

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies preliminary anti-action by pre-blocking the NKG2A-HLA-E inhibitory signaling pathway before tumor cells can establish their immune evasion mechanism. The anti-NKG2A antibody is administered to prevent the formation of the inhibitory complex between NKG2A and HLA-E, thereby preemptively enhancing NK cell killing activity before tumor cells can rely on this protective pathway

Inventive Principle:

Principle #9Preliminary anti-action

Data Source

PatentEP4644422A1Anti-NKG2a antibody and use thereof

Publication Date: 2025.11.05 BIORAY PHARMA CO LTD

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AI summary

Provided are an anti-NKG2A antibody or an antigen-binding fragment thereof and use thereof, wherein the antibody or the antigen-binding fragment thereof comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3. The antibody or the antigen-binding fragment thereof has the potential to treat tumors and provides an option for clinical medication in tumor immunotherapy.