A CCR4 antibody is an engineered protein designed to recognize and attach to a specific molecule called CCR4. By precisely binding to CCR4, these proteins can influence the behavior of cells expressing this molecule. This targeted approach forms the basis for their use in various medical treatments.
Understanding CCR4
CCR4, or C-C chemokine receptor type 4, is a protein on the surface of certain immune cells, particularly T-cells. It functions as a receptor for signaling proteins called chemokines, such as CCL17 and CCL22. The interaction between CCR4 and these chemokines guides immune cell movement to specific locations, like sites of inflammation or infection. This process, known as chemotaxis, is part of the body’s normal immune response.
CCR4 is found on various immune cell subsets, including Th2 cells and regulatory T cells (Tregs). Th2 cells are involved in allergic reactions and responses to parasites, while Tregs help to suppress immune responses and maintain immune tolerance. CCR4’s role in guiding these cells is important for immune system balance.
How CCR4 Antibodies Work
CCR4 antibodies function by specifically binding to the CCR4 protein on the cell surface. This binding can interfere with CCR4’s normal operations in several ways. One mechanism involves blocking the interaction between CCR4 and its chemokine ligands, such as CCL17 and CCL22. By preventing these chemokines from attaching, the antibody disrupts signaling pathways that direct immune cell movement and activation.
This blockade can reduce the recruitment of certain immune cells, like regulatory T cells, to specific areas. Some CCR4 antibodies are also designed to trigger an immune response against the cells they bind to. This can involve mechanisms like antibody-dependent cellular cytotoxicity (ADCC), where the antibody marks the CCR4-expressing cell for destruction by other immune cells, such as natural killer (NK) cells or macrophages.
Therapeutic Uses of CCR4 Antibodies
CCR4 antibodies are primarily used in treating certain types of T-cell cancers. CCR4 is often overexpressed on the surface of malignant T-cells in these conditions, making it a suitable target for therapy. This overexpression allows the antibody to preferentially target cancer cells while minimizing harm to healthy cells.
One notable CCR4 antibody is mogamulizumab (Poteligeo®). This humanized monoclonal antibody is approved for treating adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS), types of cutaneous T-cell lymphoma (CTCL). It also holds approval in Japan for relapsed or refractory CCR4-positive Adult T-cell Leukemia/Lymphoma (ATLL) and certain peripheral T-cell lymphomas (PTCL).
Mogamulizumab’s therapeutic effect comes from its ability to bind to CCR4 on malignant cells, leading to their elimination through antibody-dependent cellular cytotoxicity (ADCC). Its manufacturing process enhances ADCC by reducing fucose in its sugar chain structure. This mechanism targets cancerous cells and can also reduce CCR4-positive regulatory T cells, which suppress anti-tumor immune responses, thereby enhancing overall anti-tumor immunity. In clinical trials for CTCL, mogamulizumab achieved overall response rates of 37% in Sézary syndrome patients and 21% in mycosis fungoides patients, with responses lasting approximately 1 to 1.5 years.
Patient Considerations
CCR4 antibodies like mogamulizumab are administered intravenously. Initial doses are given weekly, with frequency decreasing to every other week for subsequent treatments. Before the first infusion, patients may receive pre-medications, such as antihistamines and acetaminophen, to reduce infusion-related reactions.
Patients should be monitored for side effects during treatment. Common reactions include infusion reactions, such as chills, fever, nausea, or headache. These reactions occur during or shortly after the first infusion but can also happen with later doses. Skin reactions, like rash or itching, are also observed. Distinguishing a drug-related rash from disease progression can be difficult, so medical evaluation, including a skin biopsy, may be needed. Other reported side effects include fatigue, swelling (edema), diarrhea, musculoskeletal pain, and upper respiratory infections. Patients should promptly report any new or worsening symptoms to their healthcare provider.