CD8 Binding Agents for Non-Modulating Immune Cell Recruitment

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Solution Overview

Problem

Microbial pathogens and tumor cells have developed mechanisms to evade immune destruction by cytotoxic T cells (CTLs), necessitating improved immunotherapeutic agents that can enhance anti-tumor immunity and derail tumor evasion.

Innovation Solution

Development of CD8 binding agents, such as single-domain antibodies (VHHs), that specifically bind to CD8 without modulating its function, allowing CD8-expressing cells to signal while recruiting immune cells to sites of interest, such as tumors, through additional targeting moieties like interferons or interleukins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional immunotherapeutic agents are used to enhance anti-tumor immunity, then immune cell recruitment is improved, but tumor evasion mechanisms remain effective

Engineering Contradiction:

Improveanti-tumor immunity enhancementVSAvoidtumor evasion mechanisms

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces CD8 as an intermediary target to bridge immune cells and tumor cells. The CD8 binding agent binds to CD8 on immune cells, which naturally interact with MHC class I on tumor cells, thereby mediating immune cell recruitment to tumor sites while bypassing traditional checkpoint inhibition pathways that tumors exploit for evasion

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

Instead of directly activating immune cells or blocking inhibitory checkpoints, the invention inverts the approach by targeting CD8 itself - the co-receptor that facilitates T cell recognition of tumor antigens. This indirect targeting through CD8 binding agents allows immune enhancement while avoiding direct engagement with tumor evasion mechanisms

Inventive Principle:

Principle #13The other way round (Inversion)

2Productivity

If CD8 binding agents are designed to recruit immune cells, then immune cell recruitment is improved, but CD8 signaling function may be inhibited

Engineering Contradiction:

Improveimmune cell recruitmentVSAvoidCD8 signaling function

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The CD8 binding agent is designed with specific binding characteristics that allow it to bind to CD8 at locations or in contexts that favor immune cell recruitment while preserving CD8's native signaling capability. The binding occurs in a manner that does not sterically hinder or functionally interfere with CD8's interaction with p56lck or its co-receptor function during T cell activation

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs CD8 binding agents that bind to CD8 with sufficient affinity to recruit immune cells effectively, but not so strongly as to completely block CD8 signaling. This partial occupancy or moderate affinity binding allows both immune recruitment and CD8-mediated signaling to occur simultaneously, achieving a balance between the two competing requirements

Inventive Principle:

Principle #16Partial or excessive action

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 CD8 binding agents effectively recruit immune cells to tumor sites, enhancing anti-tumor immunity and potentially treating various diseases, including cancer, infections, and immune disorders.

Implementation Method 1

these CD8 binding agents bind to, but do not functionally modulate (including, without limitation, partially or fully neutralizing) CD8

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS12448447B2CD8 binding agents

Publication Date: 2025.10.21 ORIONIS BIOSCIENCES BV

AI summary

The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.