CCR5. a chemokine receptor predominantly expressed on immune cells like T lymphocytes and macrophages, plays a pivotal role in inflammatory responses and cell migration. It gained prominence due to its co-receptor function in HIV-1 entry, where the virus binds to CD4 and CCR5 to infect host cells. The discovery of the CCR5-Δ32 mutation, which confers natural resistance to HIV in homozygous individuals, spurred interest in targeting CCR5 therapeutically.
CCR5 antibodies are monoclonal antibodies designed to block this receptor. By binding to CCR5. they inhibit HIV entry, disrupt chemokine-mediated signaling, and modulate immune cell trafficking. Notable examples include leronlimab (PRO 140), a humanized IgG4 antibody tested in HIV and COVID-19 trials. Beyond virology, CCR5 is implicated in cancer metastasis, autoimmune diseases, and graft-versus-host disease (GVHD), expanding the antibody’s potential applications.
While early clinical studies demonstrated reduced viral loads in HIV patients, challenges like viral resistance and variable efficacy persist. Emerging research explores CCR5 antibodies in combination therapies or as adjuvants in cancer immunotherapy to counteract immunosuppressive tumor microenvironments. However, safety concerns, including unintended immunosuppression, require careful evaluation. Overall, CCR5 antibodies represent a versatile tool bridging virology, oncology, and immunology, though further optimization is needed for broad clinical adoption.