Agonists induced transient heteromerization coupled to receptor internalization, while antagonists, especially plerixafor together with maraviroc, stabilized persistent surface-associated complexes. Molecular dynamics simulations in asymmetric bilayers resembling MDA-MB-231 and MCF-10A membranes identified cholesterol-enriched receptor interfaces that prolong CXCR4-CCR5 dimer lifetimes in MDA-like membranes. These results show that GPCR heteromerization is not an intrinsic fixed property of receptor pairs, but an emergent behavior shaped by cell state, lipid environment, and ligand input.

These abnormalities were ameliorated by maraviroc treatment. Collectively, CCL3 interferes with oligodendrocyte maturation, thereby delaying axonal myelination and resulting in neural circuit dysfunction mediated by VPA.

P2, N=70, Not yet recruiting, Federal University of São Paulo | Trial primary completion date: Jul 2026 --> Jan 2027

CCL5 promotes radioresistance in HNACC through maintenance of AMPK/mTOR-dependent autophagy. Targeting the CCL5/CCR5 axis enhances radiosensitivity and represents a promising therapeutic strategy.

P2, N=48, Completed, Icahn School of Medicine at Mount Sinai | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2025

P2, N=66, Active, not recruiting, CytoDyn, Inc. | Recruiting --> Active, not recruiting

P2, N=20, Recruiting, Weill Medical College of Cornell University | Not yet recruiting --> Recruiting

P1/2, N=22, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=46 --> 22

Importantly, combining CCL5-knockout CAR-T cells with the CCR5 inhibitor maraviroc significantly enhanced antitumor efficacy. These findings reveal a mechanism constraining CAR-T function in solid tumors and suggest promising combination strategies to improve therapeutic outcomes.

P2, N=20, Not yet recruiting, Weill Medical College of Cornell University

P=N/A, N=0, Available, CytoDyn, Inc.

During neoantigen vaccination, CCR5 blockade with maraviroc selectively inhibited antigen-bearing moDC migration, enhancing dendritic cell-mediated antitumor immunity. These findings showed how macrophage lineage and spatial compartmentalization govern tumor immunity and identified strategies to preserve protective IM functions, while disrupting macrophage-driven immunosuppression.