Selzentry (maraviroc) / ViiV Healthcare - LARVOL DELTA

The Dichotomy of Tumor Control by Recruited and Resident Tumor-Associated Macrophages (IMMUNOLOGY 2026) - "DC based neoantigen vaccination combined with transient CCR5 inhibition (Maraviroc) applied to assess monocyte trafficking and antigen presentation. Two major IM subsets were identified: CD206hi IMs expressing Cxcl9, Cxcl10, and Cxcl13 promoted tertiary lymphoid structure (TLS) formation, lymphocyte recruitment, and anti-tumor immunity, whereas Ccl2-expressing IMs recruited pro-tumor recMacs expressing Spp1, Vegfa, Arg1, and Cd274 (PD-L1), sustaining an immunosuppressive niche... Lung IMs display distinct spatial and functional roles in shaping the TME. Chemokine-producing CD206hi IMs sustain anti-tumor immunity, while CCL2-producing IMs and recMacs promote tumor growth. Targeting the CCL2–CCR2/CCR5 axis while preserving chemokine-producing IMs offers a promising strategy to augment cancer immunotherapy and neoantigen vaccine efficacy."

IO biomarker • Hematological Malignancies • Oncology • CCL2 • CCR2 • CXCL10 • CXCL13 • CXCL9 • MRC1 • PD-L1 • SPP1

ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION IN PATIENTS WITH HIGH-RISK ACUTE LEUKEMIAS AND HIV INFECTION (EBMT 2026) - "One patient post-allo-HCT from heterozygous CCR5 donor and Maraviroc GVHD prophylaxis discontinued ART after 8 years and HIV antibody loss (immunoblot); HIV rebound registered in 2 months and leukemia relapse in 6 months... Allo-HCT outcomes in high-risk acute leukemias with HIV comparable with general patient cohorts. ART discontinuation, even post-allo-HCT from heterozygous CCR5 donors associated with risks of HIV rebound and leukemia relapse."

Clinical • IO biomarker • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Leukemia • T Acute Lymphoblastic Leukemia • Transplantation • CCR5 • CD123 • CD4 • IL3RA

Chemokine-defined macrophage niches establish spatial organization of tumor immunity. (PubMed, Nat Immunol) - "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."

Journal • Lung Cancer • Oncology • Solid Tumor • CCL2 • CXCL10 • CXCL13 • CXCL9 • ITGAM • MRC1

Maraviroc attenuates orbital remodeling, inflammation, and lipid dysregulation in a murine model of thyroid eye disease associated with Graves' disease. (PubMed, Front Endocrinol (Lausanne)) - "Maraviroc shows promise as a targeted therapy for TED in the context of GD, offering anti-inflammatory and anti-adipogenic benefits while sparing thyroid autoimmunity. These preclinical findings support further clinical investigation into its role in managing TED."

Journal • Preclinical • Endocrine Disorders • Grave’s Disease • Immunology • Inflammation • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • CD4

Antiviral Clinical Trial for Long Covid-19 (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Trial completion date: Jan 2026 ➔ Dec 2026 | Trial primary completion date: Jan 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

Harnessing lipid-driven immunometabolic pathways in omental metastases to enhance immunotherapy in patients with ovarian cancer. (PubMed, Signal Transduct Target Ther) - "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."

IO biomarker • Journal • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD36 • SCARB1

Virtual screening and molecular fingerprinting for in silico designing of potential CCR5 inhibitors targeting HIV therapy. (PubMed, J Biomol Struct Dyn) - "Interestingly, ZINC08948076 (Mol1) and ZINC08966180 (Mol2) share similar molecular fingerprints with the drug molecule, BMS-813160. In contrast, the MD simulation trajectories revealed ZINC13150285 (Mol3) and maraviroc to have similar conformational dynamics (RMSD and Rg) between the ligand and the target protein. Additionally, ZINC24968598 (Mol4) was observed to have the lowest potential energy and ZINC09515758 (Mol5) with the lowest interaction energy. Overall, the study could identify ZINC09515758 and ZINC00673808 as potential hit molecules for further experimental investigation."

Journal • Human Immunodeficiency Virus • Infectious Disease • CXCR4

CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21. (PubMed, Front Immunol) - "We further detail past and ongoing therapeutic efforts and trials addressing these axes in both PDAC and relevant non-PDAC settings via several small-molecule antagonists and monoclonal antibodies: BMS-813160, Maraviroc, Leronlimab, FLX475, PF-07054894, IDOR- 1117-2520, and CAP-100. Despite continuous advances in the field, the current body of evidence remains limited and presents significant research gaps in areas such as spatial profiling, stage-specific analyses, and general mechanistic validation in PDAC-specific settings. Addressing these shortcomings will be key to developing a more comprehensive knowledge of the field and improving future therapeutic strategies to overcome PDAC."

IO biomarker • Journal • Review • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CCL19 • CCL2 • CCL20 • CCR2 • CCR4 • CCR6 • CCR7

Targeting ORM1-CCR5 axis inhibits the aggressive phenotype of synovial fibroblasts and alleviates RA. (PubMed, Open Med (Wars)) - "After ORM1 intervention or maraviroc treatment, the effect of ORM1 or CCR5 as well as their interplay in the stimulated cells was investigated using molecular experiments, methylthiazolyldiphenyl-tetrazolium bromide assay and transwell assay...Knockdown of ORM1 or CCR5 in CIA rats reduced arthritis index, while alleviating cartilage erosion, inflammatory infiltration and synovial hyperplasia of ankle joints. ORM1 deficiency suppresses the aggressive phenotype of FLS to reduce RA progression by downregulating CCR5."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CCR5 • ORM1

Astrocytic CCL5 orchestrates CCR5-positive neuronal necroptosis in subarachnoid hemorrhage. (PubMed, J Neuroinflammation) - "Our study unveils that astrocytic CCL5 orchestrates CCR5-dependent neuronal necroptosis via NF-κB/p-RIPK3/p-MLKL signaling, thereby driving EBI after SAH. These findings establish the CCL5/CCR5 axis as a potential therapeutic target for mitigating brain injury and cognitive dysfunction in SAH patients."

Journal • CNS Disorders • Cognitive Disorders • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • Vascular Neurology • GFAP • IL1B • TNFA

Reactive oligodendrocytes promote glioblastoma progression through CCL5/CCR5-mediated glioma stem cell maintenance. (PubMed, Neuron) - "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."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CX3CL1 • CX3CR1

HIV drug Maraviroc could be used to slow glioblastoma growth (Drug Target Review) - "A team of scientists from McMaster University and The Hospital for Sick Children (SickKids) have identified a new way to slow the growth of glioblastoma whilst also discovering an existing HIV drug that could be used as a treatment....The research shows that certain brain cells previously believed to play a purely supportive role in healthy nerve function can actively help glioblastoma tumours grow and spread. By disrupting the harmful signals sent by these cells, researchers were able to significantly slow tumour growth in laboratory models."

Preclinical • Glioblastoma

MARAVIROC: This Study is Assessing the Safety and Efficacy of Immune Inhibition as a Treatment to Prevent Primary Graft Dysfunction (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: University of California, San Francisco | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2025 ➔ Dec 2025

Enrollment open • Trial initiation date • Acute Lung Injury • Respiratory Diseases • Transplantation

Toxoplasma effector GRA15-driven CCL5 secretion enhances brain parasite load through microvascular sequestration of phagocytes. (PubMed, mBio) - "Pretreatment of mice with recombinant CCL5 dramatically elevated the sequestration of infected DCs, while treatment with the selective chemokine receptor 5 (CCR5) antagonist Maraviroc reverted sequestration...When the effect of CCL5 was pharmacologically blocked, fewer infected cells sequestered in the brain vessels, lowering the parasite loads. These findings reveal a mechanism through which Toxoplasma manipulates host cells to produce factors that facilitate its colonization of the brain."

Journal • Infectious Disease • CCL5

Inflammatory mediators differentially regulate megakaryopoiesis and thrombopoiesis in myelofibrosis and essential thrombocythemia. (PubMed, Sci Rep) - "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."

Journal • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • BCL2L1 • CD34 • IL1B • IL6 • JAK1

SOCS1 in graft CD8+ T cells ameliorates intestinal aGVHD by modulating chemokine-driven monocyte-to-M1 macrophage polarization (ASH 2025) - "Concurrently, the M1-to-M2 transition seen in WT crypt macrophages was impaired in thecKO group, with persistent pro-inflammatory M1 profiles.Pharmacologic intervention using Ruxolitinib (JAK1/2 inhibitor) or Maraviroc (CCR5 antagonist) alleviated intestinalinflammation in cKO GVHD models. These findingsconfirm that SOCS1 regulates GVHD severity by modulating both CD8⁺ T cell activation and downstream macrophagepolarization via the JAK/STAT–CCL5 axis.In clinical datasets, high SOCS1 expression in graft-derived CD8⁺ T cells correlated inversely with expression of JAK/STATtargets and chemokine pathway components, and was associated with a reduced risk of GVHD. These data indicate thatSOCS1 is a key regulator of immune homeostasis following allo-HSCT, and suggest its potential use as a predictivebiomarker and therapeutic target for GVHD prevention."

Acute Graft versus Host Disease • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Inflammation • Inflammatory Bowel Disease • CCR1 • CD8 • CXCR3 • GZMB • IFNG • ITGAE • LAMP1 • MRC1 • PRF1 • SOCS1 • STAT1 • STAT2 • TGFB1 • TNFA • TNFSF13 • TOP2A

CCR5 blockade: A therapeutic approach to uncouple CART-BCMA expansion from CART-mediated immune toxicities. (ASH 2025) - "CirAE are associated with elevated CARTexpansion in the first two weeks, suggesting that modulating CART-BCMA proliferation without affectingCART effector function could improve safety and expand therapeutic use. We retrospectively analyzed a cohort of 198 multiple myeloma (MM) patients treated with CART-BCMA (idecabtagene vicleucel [ide-cel] and ciltacabtagene autoleucel [cilta-cel]) at the University ofPennsylvania (June 2021-December 2024) to identify predictors of CirAE and to investigate themechanisms underlying the early onset of CirAE...Finally, CCR5 knockout impaired antigen-driven proliferation and rendered CART insensitive to maraviroc, confirming on-target specificity. We identified the IL‑15–CCL5–CCR5 circuit as a key driver of CART-BCMA proliferation inCirAE and demonstrated that CCR5 blockade safely restrains CART-BCMA expansion while preservingtheir anti‑myeloma activity. These findings support CCR5-directed targeted strategies to selectivelymodulate CART..."

IO biomarker • CNS Disorders • Gastrointestinal Disorder • Hematological Malignancies • Multiple Myeloma • CD4 • CD8 • CXCL10 • CXCL9 • GZMB • IL15 • IL2 • IL7 • LAMP1

Intensification with a CCR5 inhibitor at ART initiation Modulates IL-18 and Inflammation-Driven Immune Pathways in People with HIV. (PubMed, Int J Infect Dis) - "Our results suggest that MVC intensification at ART initiation might contribute to reducing IL-18 levels and inflammation-driven immune pathways, providing insights for strategies to mitigate persistent inflammation in PWH."

Journal • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CCL19 • CXCL10 • CXCL9 • IFNG • IL18

Cell-free secretome of CD56brightCD16bright directly reprogrammed NK cells enhances wound healing via CCL3/4/5-CCR5 signaling. (PubMed, Theranostics) - "Notably, CCR5 inhibition by maraviroc abrogated drNK-CM-induced cell migration and delayed wound closure in vivo, highlighting the central role of the CCL3/4/5-CCR5 axis...The reparative effects are primarily mediated via the CCL3/4/5-CCR5 signaling axis and pro-angiogenic cascades. Given their consistent phenotype and reproducible secretome, drNKs represent a scalable and safe source for cell-free regenerative therapeutics."

Journal • CCL3 • CCR3 • KLF4 • POU5F1 • SOX2

A CD25-chemokine receptor complex initiates non-canonical IL-2 signaling. (PubMed, J Biol Chem) - "In contrast, IL-2(E52K) supported activation in CCR5Hi IL-2Rα+ YT-1 cells which was blocked by the CCR5-specific antagonist, Maraviroc...Thus, both anti-CD25 antibody and HS require formation of a chemokine receptor-CD25 complex to initiate alternative IL-2 signaling. In addition, our findings suggest that alternative and canonical IL-2 signaling receptors can be incorporated into the same multi-protein assembly, allowing for a single complex to mediate divergent effects on downstream signaling."

Journal • CCR7 • CD4 • CXCR4 • FCGR2A • FCGR2B • IL2 • IL2RA • IL2RG • ISG20

Distinct memory CD4+ T cell subset tropism of two CCR5-tropic HIV-1 in a rapid progressor. (PubMed, ASM Case Rep) - "The T/F virus is more than 100-fold more resistant to the CCR5 inhibitor Maraviroc than the superinfecting virus. This case report demonstrates that CCR5 HIV-1 variants have distinct memory CD4+ T cell subset preferences in vivo. Because CD4+ T cell subset targeting is highly relevant for HIV-1 pathogenesis, understanding the underlying molecular mechanisms may provide deeper insights into HIV-1 therapeutics and functional cure."

Journal • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease • CD4

WITHDRAWN Genetic signatures in the highly virulent subtype B HIV-1 conferring immune escape to V1/V2 and V3 broadly neutralizing antibodies (ASTMH 2025) - "Co-receptor usage and Maraviroc sensitivity were evaluated in NP-2 cell lines and primary CD4+ T cells to confirm viral entry pathways and potential drug inhibition.We found that the absence of N295 and N332 glycans in the high-mannose patch, which are crucial for neutralization by V3 glycan bNAbs and are typically conserved in subtype B HIV-1, is a notable feature in more than half of the VB variants...Additionally, all VB variants investigated had an insertion in V2, contributing to immune escape from the V1/V2 bNAbs PG9 and PG16. These findings suggest the potential co-evolution of HIV-1 virulence and antigenicity, underscoring the need to monitor both the viral pathogenicity and neutralization susceptibility of newly emerged HIV-1 strains."

Human Immunodeficiency Virus • Infectious Disease • CD4

Single-cell transcriptomics unravels the early immune landscape of renal allograft rejection and nominates Ccl3-Ccr5 as a therapeutic target. (PubMed, Front Immunol) - "Our study establishes an in-depth, early-stage immune landscape of renal transplantation, revealed that the Isg15+Mac subset activates T cells via the Ccl3-Ccr5 axis and thereby serves as a critical driver of acute rejection. And indicating that Maraviroc may potentially be a therapeutic candidate for transplant rejection."

Journal • Immunology • Nephrology • Transplant Rejection • Transplantation • CCL3 • PTPRC

RAP-103, a multi-chemokine receptor antagonist, displays anxiolytic-like effects and normalizes methamphetamine abstinence-induced behaviors in planarians. (PubMed, Physiol Behav) - "Maraviroc (1, 10 μM), a CCR5 antagonist, decreased light avoidance (like RAP-103) but reduced motility. RAP-103 (0.01, 0.1, 1 μM), administered during METH abstinence, counteracted METH-induced light avoidance but did not rescue METH-induced motility deficits. Our results with planarians show that RAP-103 displays anxiolytic-like and motor-enhancing effects and counteracts METH abstinence-induced behaviors, highlighting the potential of RAP-103 as a chemokine-based CNS therapeutic."

Journal • CCR2 • CCR8

Targeting the CCL5/CCR5 axis in tumor-stromal crosstalk to overcome cisplatin resistance in neuroendocrine prostate cancer. (PubMed, J Exp Clin Cancer Res) - "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."

Journal • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • CAFs • STING