carlumab (CNTO 888) / J&J, Novartis - LARVOL DELTA

Analysis of hub genes temporal dynamics in cardiac ischemia/reperfusion injury: a bioinformatics and experimental study. (PubMed, Front Physiol) - "Degree algorithm analysis identified the top ten hub genes (Il1b, Cxcl2, Cd44, etc.) at 6h, (Il1b, Il6, Fn1, etc.), at 24 h and (Fcgr3, Ccl2, Cd68, etc.) at 72 h. Most hub genes showed notable interactions with specific microRNAs (mmu-let-7c-1-3p, mmu-miR-466L-3p), the transcription factor Nfkb1, and drugs with the highest drug-gene interaction scores (EMAPTICAP PEGOL, CARLUMAB, Compound 27 [PMID: 19854648]). Validation in HL-1 OGD/R models and external datasets confirmed elevated mRNA expression of Serpine1, Ccl2, Il6, and Fn1 at various reperfusion stages. Analysis across multiple datasets and HL-1 cell experimental models revealed four significantly altered genes-Serpine1, Ccl2, Il6 and Fn1-indicating their potential targets for MIRI."

Journal • Cardiovascular • Coronary Artery Disease • Myocardial Ischemia • Reperfusion Injury • CCL2 • CD68 • FCGR3A • IL1B • IL6 • Let-7c • SERPINE1

Antagonism of estrogen-related receptor-α inhibits mitochondrial oxidative phosphorylation and reduces M2 macrophage infiltration in endometrial cancer. (PubMed, J Immunother Cancer) - "This study uncovers a pivotal role of the ERRα metabolic axis in reshaping the EC immune microenvironment, providing the mechanistic evidence linking mitochondrial lipid metabolism to macrophage-driven immunosuppression. Our findings establish a theoretical foundation for developing combination therapies targeting metabolic-immune crosstalk, offering a strategy to overcome immunotherapy resistance in EC."

IO biomarker • Journal • Endometrial Cancer • Metabolic Disorders • Oncology • Solid Tumor • CCL2 • PTPMT1

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets. (PubMed, Front Immunol) - "Potential RNA regulatory pathways, including MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1, contribute to our knowledge of SSc. Furthermore, the analysis of drug-hub gene interactions predicted TIPLASININ, CARLUMAB and BINDARIT as candidate drugs for SSc."

Journal • Fibrosis • Hematological Disorders • Immunology • Scleroderma • Systemic Sclerosis • CCL2 • IL6 • ISG15 • MALAT1 • MIR206 • SERPINE1

Computational Drug Discovery in Ankylosing Spondylitis-induced Osteoporosis Based on Data Mining and bioinformatics analysis. (PubMed, World Neurosurg) - "In conclusion, CARLUMAB, BERMEKIMAB, RILONACEPT, RILOTUMUMAB and FICLATUZUMAB were first identified as the potential drugs for the treatment of AS-OP, proving the value of text mining and pathway analysis in drug discovery."

Journal • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Orthopedics • Osteoporosis • Rheumatology • Seronegative Spondyloarthropathies

[VIRTUAL] Inhibition of C-C Motif Chemokine Ligand 2 with Chemotherapy Prolongs Survival in a Minimal Residual Disease Mouse Model of Metastatic Neuroblastoma (AAP-NCE 2021) - "Mice were divided into four cohorts: untreated control, anti-CCL2 antibody alone (Carlumab, Janssen Pharmaceuticals, NJ,USA), etoposide alone, and anti-CCL2 antibody+etoposide. Our in vitro studies show that CCL2 production by monocytes is augmented by neuroblastoma cells, and that increasing concentrations of CCL2 leads to increased migration of NB cells, suggesting a positive feedback loop for metastatic disease in NB. In vivo, anti-CCL2 antibody combined with chemotherapy significantly increases survival in our MRD mouse model of recurrent metastatic disease. Inhibition of CCL2 may represent a novel treatment strategy to target recurrent metastatic disease in neuroblastoma."

Minimal residual disease • Preclinical • Residual disease • Immunology • Inflammation • Neuroblastoma • Oncology • Solid Tumor • CCL2

A study to evaluate the safety and effectiveness of CNTO 888 administered intravenously (IV) in subjects with idiopathic pulmonary fibrosis (IPF) (clinicaltrials.gov) - P2, N=126; Active, not recruiting -> Terminated (DMC recommended stopping two highest dose groups, Sponsor decided to stop dosing completely); Completion date: Jun 2012 -> Jan 2012

Completion date • Trial terminated • Fibrosis

A phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of the safety and efficacy of CNTO 888 (carlumab) in patients with idiopathic pulmonary fibrosis, [Publication Page: A3376] (ATS 2013) - Presentation time: 10:45 AM - 12:30 PM, Monday, May 20, 2013; Poster Board # A30; P2, N=126; NCT00786201; Sponsor: Centocor, Inc.; "The rate of percent change in FVC through Week 52 showed no treatment effect (placebo, -0.58; 1mg/kg, -0.53; 5mg/kg, -0.80; 15mg/kg, -0.47; p=0.261). Time to disease progression was similar in the 1, 5, and 15 mg/kgcarlumab groups compared to placebo (HR[95%CI], 1.08 [0.24, 4.86], 1.98 [0.51, 7.72], and 0.85 [0.17, 4.26]), respectively...Carlumab had no measureable benefit in patients with IPF."

P2 data • Fibrosis

Annual report 2012 (Morphosys) - "In 2012, Janssen Biotech discontinued the development of the antibody CNTO888 in the areas of cancer and idiopathic pulmonary fibrosis."

Discontinued • Fibrosis

Predictors of mortality in idiopathic pulmonary fibrosis: Results from 72 week phase II study of CNTO888 (carlumab), [Publication Page: A3377] (ATS 2013) - Presentation time: 10:45 AM - 12:30 PM, Monday, May 20, 2013; Poster Board # A31; P2, N=126; NCT00786201; Sponsor: Centocor, Inc.; "...the final regression model demonstrated the use of OCS at baseline was associated with a significant increased risk of death (OR 5.7, 95% CI 1.5-21.1). Patients with 6MWD of <260m had the highest risk of death (OR: 14.6, 95% CI: 3.7-58.0). Neither high risk status (OR: 1.9, 95% CI: 0.5-7.1) nor carlumab treatment (OR: 0.40 95% CI: 0.12-1.32) were significantly associated with mortality. DLCO and SGRQ were no longer significant in the logistic regression analysis."

P2 data • Fibrosis

CCL2/12 from Injured Alveolar Epithelial Cells Initiated and Promoted Progressive Pulmonary Fibrosis (ATS 2019) - "...However, a recent phase 2 clinical trial of carlumab, a human IgG1κ mAb with high affinity and specificity for human CCL2, failed on the treatment of Idiopathic pulmonary fibrosis (IPF) patients...Surprisingly, mice with complete deletion of CCL12 were not protected from pulmonary fibrosis in the bleomycin model and demonstrated marked increase in expression of other CCR2 ligands...Together our data suggest that injury leads to alveolar epithelial cell derived CCL2/CCL12 production which recruits bone marrow derived macrophages to the lung where upon efferocytosis of apoptotic alveolar epithelial cells they promote activation of fibrosis. Upregulation of expression of other CCR2 ligands may be due to CCL2/CCL12 expression by cells other than alveolar epithelial cells potentially offering better insight into more effective inhibition of this pathway."