Humanized Anti-CCR4 Antibodies for Treg Migration Blockade

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Solution Overview

Problem

Current therapies for cutaneous T cell lymphoma (CTCL) are palliative and do not achieve durable remissions, and there is a need for more effective treatments due to immune dysfunction and suppression of effector T-cells by regulatory T-cells through the chemokine receptor CCR4.

Innovation Solution

Development of a humanized monoclonal antibody against CCR4 with an IgG4 heavy chain region that inhibits the migration of regulatory T-cells and enhances effector T-cell activity, potentially linked to therapeutic agents or cytokines, to modulate immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current palliative therapies are used for CTCL, then treatment can be administered, but durable remissions are not achieved and treatment effectiveness is limited

Engineering Contradiction:

Improvedurable remissionVSAvoidtreatment effectiveness

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent introduces a humanized anti-CCR4 monoclonal antibody as an intermediary agent that blocks the interaction between CCR4 receptors on regulatory T-cells and their ligands, thereby preventing Treg-mediated suppression of effector T-cells and enabling durable remissions in CTCL patients

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the antibody structure by humanizing the anti-CCR4 monoclonal antibody and selecting specific IgG subclasses (IgG1, IgG2, or IgG4) to optimize effector functions such as complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, thereby enhancing treatment effectiveness

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If regulatory T-cells migrate to tumor sites through CCR4 signaling, then immune suppression is enhanced, but effector T-cell activity is reduced

Engineering Contradiction:

ImproveTreg suppressionVSAvoideffector T-cell activity

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent extracts and blocks the specific CCR4 signaling pathway that mediates regulatory T-cell migration and suppressive function, thereby removing the harmful suppressive effect while preserving effector T-cell activity against tumor cells

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The anti-CCR4 monoclonal antibody serves as an intermediary that interferes with the binding between CCR4 receptors and their ligands (CCL17/TARC and CCL22/MDC), preventing regulatory T-cell recruitment to tumor sites and their subsequent suppressive activity

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250339521A1Humanized CC chemokine receptor 4 (CCR4) antibodies and methods of use thereof

Publication Date: 2025.11.06 DANA FARBER CANCER INSTITUTE INC

AI summary

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4− IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab aim exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of a cancer.