CD8-Binding VHH Polypeptides for Targeted T-Cell Activation

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for CD8-binding polypeptides that can specifically target activating molecules to CD8+ T cells to increase the potency and selectivity of cytotoxic T cell responses, particularly for treating cancer.

Innovation Solution

CD8-binding polypeptides comprising VHH domains with specific CDR sequences and optionally fused with cytokines like IL-2, IL-15, or other antigen-binding domains, designed to enhance T cell activation and targeting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional T cell activation methods are used, then T cell activation occurs, but selectivity and potency are insufficient for targeted cancer therapy

Engineering Contradiction:

Improveselectivity of cytotoxic T cell responsesVSAvoidpotency of cytotoxic T cell responses

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent introduces CD8-binding polypeptides as intermediary molecules that specifically bind to CD8 on cytotoxic T cells and recruit activating molecules such as cytokines or co-stimulatory signals. This mediator approach enables selective targeting of CD8+ T cells with high potency while maintaining specificity, resolving the contradiction between selectivity and potency in cancer therapy.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If CD8-binding polypeptides with additional binding domains are designed, then selectivity increases, but molecular complexity increases

Engineering Contradiction:

Improvespecificity of T cell targetingVSAvoidpolypeptide structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple functional domains into single polypeptide constructs: a CD8-binding domain (VHH or scFv) is combined with cytokine domains (such as IL-2, IL-15, or IL-7) or co-stimulatory domains within a single polypeptide chain. This merging approach increases targeting specificity while managing complexity through modular design, allowing the polypeptide to simultaneously bind CD8 and deliver activating signals.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The CD8-binding polypeptides are designed with multi-functionality, serving as both targeting vectors and activating agents. The same polypeptide structure that binds CD8 also contains embedded cytokine or co-stimulatory domains that provide activating signals, eliminating the need for separate targeting and activation components and thereby managing complexity while enhancing specificity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If fusion polypeptides with cytokines are used, then T cell activation potency increases, but risk of off-target effects increases

Engineering Contradiction:

ImproveT cell proliferation and cytotoxic activityVSAvoidoff-target effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by confining cytokine activity to the immediate vicinity of CD8+ T cells through CD8-targeted delivery. The cytokine domains are embedded within CD8-binding polypeptides, ensuring that cytokine release and activity are localized specifically to cells expressing CD8. This localized delivery enhances T cell activation potency while minimizing off-target effects on non-CD8+ cells, thereby resolving the contradiction between productivity and harmful effects.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250320295A1CD8-Binding Polypeptides and Uses Thereof

Publication Date: 2025.10.16 INHIBRX BIOSCIENCES INC

AI summary

Provided herein are VHH-containing polypeptides that bind CD8. Uses of the VHH-containing polypeptides are also provided.