CCR4 (C-C chemokine receptor type 4) is a G protein-coupled receptor expressed on immune cells, including Th2 cells, regulatory T cells (Tregs), and certain malignancies. It binds chemokines CCL17 and CCL22. playing a key role in cell migration and immune regulation. In cancer, CCR4 is often overexpressed in aggressive T-cell lymphomas (e.g., adult T-cell leukemia/lymphoma) and solid tumors, where it facilitates tumor cell trafficking and immune evasion by recruiting immunosuppressive Tregs into the tumor microenvironment.
Therapeutic CCR4 antibodies, such as mogamulizumab, are designed to target and block CCR4 signaling. Mogamulizumab, a humanized monoclonal antibody, received FDA approval in 2018 for relapsed/refractory mycosis fungoides or Sézary syndrome. It works via antibody-dependent cellular cytotoxicity (ADCC), selectively depleting CCR4-positive malignant cells. However, CCR4 inhibition may also affect normal immune cells, potentially leading to autoimmune or infectious complications.
Research continues to explore CCR4's role in other diseases, including autoimmune disorders and HIV infection, where CCR4 serves as a co-receptor for viral entry. Challenges include optimizing specificity to minimize off-target effects and overcoming resistance mechanisms. Dual-targeting strategies and combination therapies with checkpoint inhibitors are under investigation to enhance efficacy in both hematologic and solid cancers. CCR4 remains a promising but complex therapeutic target in immuno-oncology.