AntiCCR4

AntiCCR4 refers to monoclonal antibodies that target the chemokine receptor CCR4, a cell surface protein expressed on certain T-cell subsets, including some malignant T cells in specific lymphomas and regulatory T cells. By binding CCR4, these antibodies can recruit immune effector mechanisms such as antibody-dependent cellular cytotoxicity to kill CCR4-expressing cells and may deplete regulatory T cells in the tumor microenvironment, potentially enhancing anti-tumor responses while carrying risks of immune-related effects.

Clinical use and examples: The most well-known anti-CCR4 antibody is mogamulizumab, a humanized monoclonal antibody used in various regions for CCR4-positive cutaneous T-cell lymphomas such as mycosis fungoides and Sézary syndrome, and for certain CCR4-expressing adult T-cell leukemia/lymphoma. Indications and approvals vary by country, and other anti-CCR4 antibodies have been investigated in clinical trials for similar or broader indications.

Mechanism and rationale: Targeting CCR4 aims to selectively eliminate CCR4-expressing malignant T cells and reduce populations of regulatory T cells that can support tumor growth. The therapeutic effect is often mediated by Fc-dependent mechanisms, most notably ADCC, and may be influenced by the density of CCR4 expression on tumor cells and the balance of immune cell subsets in the patient.

Safety and considerations: Common adverse events include infusion reactions, skin rashes and pruritus, fatigue, and cytopenias. Depletion of regulatory T cells can raise concerns about infections and autoimmune phenomena, and in certain clinical scenarios (such as prior to stem cell transplantation or in HTLV-1–endemic areas) may affect graft-versus-host disease risk. Ongoing research explores combinations with other therapies and the development of additional anti-CCR4 agents.