Selzentry (maraviroc) / ViiV Healthcare - LARVOL DELTA

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

Antiretroviral Therapy Intensification With Dolutegravir and/or Maraviroc Did Not Affect HIV-1 Cell-Associated DNA, RNA, and 2--LTR Circles Over 12 Weeks. (PubMed, Open Forum Infect Dis) - "DTG + MVC intensification reduced ca2LTR detection at weeks 2-4, though this effect did not persist through week 12. These findings indicate the minimal impact of intensification on the HIV-1 peripheral reservoir, consistent with prior studies."

Clinical • Journal • Alzheimer's Disease • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease

Genotypic susceptibility to broadly neutralizing antibodies and fostemsavir of transmitted viruses, and evolution over time in the French acute HIV infection PRIMO cohort (EACS 2025) - "Method : We analyzed 191 sequences from participants in the acute infection French ANRS PRIMO cohort, over 3 decades (1988–2022), using sequence-based algorithms to predict susceptibility to teropavimab (3BNC117), zinlirvimab (10-1074) and entry inhibitors (fostemsavir, maraviroc). Conclusions : These findings underscore the importance of continuous surveillance of transmitted viruses to therapies targeting HIV-1 Env. Integrating phenotypic assessment with genotypic surveillance to refine resistance prediction models will also be important for predicting susceptibility, as well as the correlation with clinical efficacy in ongoing trials."

Human Immunodeficiency Virus • Infectious Disease • CD4

A French national real-world observatory of people initiating a lenacapavir-based treatment during the post-approval period (EACS 2025) - "No emergence of DRMs was observed for drugs of the background regimen except a switch to X4 tropism in a participant receiving maraviroc. Conclusions : In this study, PWH receiving LEN-based treatment harbored multidrug-resistant viruses with limited treatment options, and half of PWH were virologically-suppressed at LEN initiation. Virological success was achieved in 63% of PWH with quantifiable VL at LEN initiation, and maintained in 95% of virologically-suppressed PWH."

Clinical • Real-world • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY OCCURRING UNDER NATALUZIMAB TREATMENT; CLINICAL AND RADIOLOGICAL FEATURES (WCN 2025) - "The most important limiting factor regarding the use of NTZ is the Progressive Multifocal Leukoencephalopathy (PML) case that develops in individuals with John Cunningham (JC) virus seropositivity. In this study, we present the clinical and radiological features of our patient who developed PML during NTZ use. A 56-year-old woman was started on Natalizumab treatment in May 2021. It should not be forgotten that there is a higher risk of PML for patients when the index becomes positive."

Clinical • CNS Disorders

Targeting the CCL5-CCR5 Axis: A New Strategy Against Chemoresistant Mesothelioma (IMIG 2025) - "Although immunotherapy has emerged as a first-line treatment, many patients develop resistance, leaving chemotherapy (pemetrexed and cisplatin) as the second-line standard of care...Similarly, treatment with Maraviroc in mice injected with resistant cells reduced tumour growth and macrophage infiltration within the tumour microenvironment.• Conclusion This study highlights the CCL5-CCR5 axis as a key driver of cisplatin resistance in malignant pleural mesothelioma. By promoting the recruitment of pro-tumour macrophages, CCL5 contributes to an immunosuppressive microenvironment supporting tumour growth. Targeting this pathway, either genetically or pharmacologically, effectively reduces tumour progression, positioning CCL5-CCR5 as a promising therapeutic target to overcome chemoresistance."

IO biomarker • Malignant Pleural Mesothelioma • Mesothelioma • Pleural Mesothelioma • Solid Tumor • CCL5 • CCR5 • MRC1

Effect of RANTES on Vascular Contractile and Relaxant Responses in Rat Carotid Arteries. (PubMed, Biol Pharm Bull) - "However, RANTES treatment impaired acetylcholine-induced relaxation, whereas relaxations induced by the nitric oxide donor sodium nitroprusside, the ATP-sensitive potassium channel activator cromakalim, and the large-conductance calcium-activated potassium channel activator NS19504 were unaffected...Furthermore, the cyclooxygenase inhibitor indomethacin also abolished the differences in acetylcholine-induced relaxation between the 2 groups. Co-treatment with the antioxidant N-acetyl-l-cysteine enhanced acetylcholine-induced relaxation in the presence of RANTES, while co-treatment with the C-C motif chemokine receptor 5 antagonist maraviroc slightly improved the relaxation response. These findings suggest that RANTES impairs acetylcholine-induced relaxation, likely due to the reduction of nitric oxide bioavailability and the unmasking of vasoconstrictor prostanoids through increased reactive oxygen species."

Journal • Preclinical • CCR5 • EDN1

C-C motif glycoprotein ligand 5 (CCL5) and its GPCR CCR5: Macromolecular game-changers in cancer biology. (PubMed, Int J Biol Macromol) - "Translational techniques employing CCR5 antagonists such as Maraviroc, GAG-binding modulators, glycoengineered CCL5 variants, delivery systems, and their integration with immune checkpoint inhibitors (ICIs) and targeted therapies are highlighted for their considerable therapeutic promise. Critical research priorities, encompassing single-cell phenotyping, CRISPR-mediated screening of chemokine pathways, and structural-functional mapping, are outlined to facilitate precise modulation of the CCL5/CCR5 axis in targeted cancer therapy. This review addresses structural biology and tumor immunology to identify the CCL5/CCR5 axis as a multifaceted yet promising biological target for innovative cancer therapeutics."

Journal • Review • Immunology • Oncology • CD8 • PD-L1

The Mechanism of Immunotherapeutic Resistance in Pulmonary Sarcomatoid Carcinoma (IASLC-WCLC 2025) - "Experimental mice were divided into four groups, with the exposure of following drugs: IPG1576 (MIF inhibitor; 10 mg/kg, i.p., q2d), BX471 (CCR1 antagonist; 50 mg/kg, s.c., q2d), Camrelizumab, Ociperlimab and Maraviroc [CCR5 antagonist] (all 10 mg/kg, i.p., q3d). In humanized PDX models (Fig.1M), the CCR1/CCR5 inhibitor combination (G4) outperformed MIF inhibitor/ anti-TIGIT (G3) (Figs.1O-P), reversing resistance by increasing precursor-exhausted and reducing terminal-exhausted CD8+ T cells (Fig.1Q). These findings identify CCR1/CCR5 blockade as a novel strategy to reverse immunotherapeutic resistance in PSC Conclusions : The additional combination of CCR1/CCR5 blockade with anti-PD-1 demonstrated a synergistic efficacy to immunotherapy-resistant tumors via reshaping the microenvironment, potentially offering a novel approach to combat immunotherapy resistance in PSC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • CCL3 • CD8 • CXCL10 • CXCL5 • GZMK • LDHB • NECTIN2 • SLC8A1 • TIGIT

C-C chemokine receptor type 5 activation stimulates adipocyte differentiation through ERK-dependent pathway. (PubMed, Int J Med Sci) - "Moreover, pretreatment with the CCR5 inhibitor maraviroc and the ERK inhibitor PD98059 significantly reduced RANTES-induced adipocyte differentiation. In vivo, WT mice on a high-fat diet showed higher plasma RANTES levels and increased adipose CCR5 expression, as well as obesity, whereas these changes were absent in CCR5-/- mice. The results suggest that CCR5 activation by RANTES enhances adipocyte differentiation via an ERK-dependent pathway, and that CCR5 plays a critical role in the development of obesity."

Journal • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • CCR5 • PPARG

Spatial Crosstalk Modeling of the Tumor Microenvironment Identifies CCR5-Mediated Glia-to-Glia Signaling as a Key Regulator of Brain Metastatic Progression. (PubMed, Cancer Res) - "Therapeutic targeting of CCL4-CCR5 signaling with maraviroc, an FDA-approved antiviral drug, significantly reduced brain metastasis progression without exerting direct cytotoxic effects on tumor cells. These findings highlight a promising therapeutic strategy that focuses on modulating glial communication within the tumor microenvironment. By disrupting the supportive glial niche rather than targeting tumor cells directly, this represents a distinct and potentially less toxic approach for managing brain metastases."

Biomarker • Journal • Oncology • Solid Tumor • CXCL16 • CXCR6 • IL1A • IL1R1 • OSMR

Omadacycline in the treatment of severe Q fever pneumonia during an influenza epidemic: a case report with literature review. (PubMed, Front Med (Lausanne)) - "Following antiviral treatment with Maraviroc and antibiotic therapy with omadacycline tosilate (a novel tetracycline-class drug) for Coxiella burnetii infection, the patient's clinical symptoms improved, biochemical markers normalized, and pulmonary imaging showed resolution. This case highlights the potential of tNGS to improve the detection rate of mixed infections in cases of severe pneumonia of unknown etiology. The novel tetracycline drug, such as omadacycline, has demonstrated efficacy against Q fever rickettsial pneumonia, offering a new perspective for clinical diagnosis and treatment."

Journal • Infectious Disease • Influenza • Pneumonia • Respiratory Diseases

Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Antiretrovirals (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: Federal University of São Paulo | Phase classification: P=N/A ➔ P2

Phase classification • Human Immunodeficiency Virus • Infectious Disease • IL4

MASTER: Manipulating the Peri-Infarct Area Using Maraviroc to Enhance Motor Skills After Stroke (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Emmanuel Carrera

New P2 trial • Cardiovascular • Ischemic stroke

MASTER: Manipulating the Peri-Infarct Area Using Maraviroc to Enhance Motor Skills After Stroke (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Emmanuel Carrera | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target. (PubMed, Inflammopharmacology) - "With therapeutic inhibition of CCR5 gaining attention, Maraviroc is approved for HIV treatment, while monoclonal antibodies such as leronlimab, genetic strategies (CRISPR), and dual CCR2/CCR5 antagonists such as cenicriviroc are under investigation for broader applications. Blocking CCR5 has shown efficacy in reducing metastasis and improving chemotherapy outcomes, reinforcing its therapeutic potential. Along with CCR5's role in disease pathogenesis, emphasizing its involvement in immune regulation and inflammatory processes, this review explores the multifaceted role of CCR5 in immunity, its contribution to disease pathogenesis, and innovative therapeutic interventions targeting CCR5 to modulate immune responses and treat diseases."

Journal • Review • Atherosclerosis • Breast Cancer • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • HER2 Breast Cancer • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Rheumatoid Arthritis • Rheumatology • Solid Tumor • CCL3 • CCR2 • CCR5 • HER-2