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.

P2, N=90, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Jan 2026 --> Dec 2026 | Trial primary completion date: Jan 2026 --> Nov 2026

Pharmacological modulation of lipid-driven signaling pathways through CCR5 inhibition (inflammation modulation through maraviroc) or blockade of the lipid scavenger receptor CD36 reprograms TAMs, restores T cell activity, and enhances antitumor immune responses within lipid-rich tumor niches...Consistent with these mechanistic insights, we demonstrated that the specific immunometabolic niche in omental metastases is clinically associated with responsiveness to ICB. We propose a non-invasive radiomics and machine-learning-based analysis of imaging data to assess omental involvement for patient stratification.

P2, N=16, Completed, CytoDyn, Inc. | N=30 --> 16 | Trial completion date: Jul 2022 --> Jan 2025 | Active, not recruiting --> Completed

Targeting CCR5 with genetic knockdown or the approved drug maraviroc impairs GSC stemness and prolongs survival in GBM models. Our work highlights the functional interplay between OLs and GBM cells and positions the CCL5/CCR5 axis as a druggable target in GBM.

P2, N=120, Recruiting, University of California, San Francisco | Not yet recruiting --> Recruiting | Initiation date: Jun 2025 --> Dec 2025

MF plasma increased megakaryocyte output, which was attenuated in sequential samples from ruxolitinib-treated patients...Elevated levels of circulating RANTES correlated with ET plasma-induced proplatelet formation, which was partially reverted by RANTES receptor CCR5 antagonist Maraviroc, indicating RANTES is involved in this process. These findings indicate that, in addition to clonal mutations, extrinsic inflammatory mediators play a direct role in MF and ET megakaryocyte abnormalities. The distinct cytokine profile could potentially be useful for the development of targeted therapies.

P2/3, N=43, Terminated, CytoDyn, Inc. | Active, not recruiting --> Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

P2/3, N=56, Terminated, CytoDyn, Inc. | Active, not recruiting --> Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

Our findings identify the CCL5/CCR5 axis as a key mediator of tumor-stromal crosstalk driving cisplatin resistance in NEPC. Mechanistically, CAF-derived CCL5 activates AKT signaling in tumor cells by promoting the formation of the CCR5/β-arrestin1/p85 complex. Targeting this pathway with maraviroc in combination with cisplatin offers a promising therapeutic strategy for overcoming drug resistance in NEPC.

P1/2, N=332, Completed, Bristol-Myers Squibb | Phase classification: P1b/2 --> P1/2

P2, N=20, Terminated, CytoDyn, Inc. | Active, not recruiting --> Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.