Carlumab

Carlumab (alternate identifier CNTO 888[1]) is a discontinued human recombinant monoclonal antibody (type IgG1 kappa)[2] that targets human CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein (MCP1).[3][4][5] Carlumab was under development for use in the treatment of oncology and immune indications[6][7] and was studied for application in systemic sclerosis, atherosclerosis, diabetic nephropathy, liver fibrosis and type 2 diabetes.[2]

Carlumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetMCP-1
Clinical data
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6442H9966N1706O2018S40
Molar mass144884.91 g·mol−1
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The inhibitory binding of Carlumab to CCL2 was hypothesized to inhibit angiogenesis and consequently modulate tumor cell proliferation.[3][2] Studies focusing on the effects of Carlumab have been performed in vitro on cell lines and in vivo on mice and in humans including phase 1 and phase 2 clinical trials evaluating the efficacy, safety and dose requirements of the drug. Clinical trials for Carlumab include studies of idiopathic pulmonary fibrosis,[8][9] castration-resistant metastatic prostate cancer[1][10] and solid tumors.[11][12]

Carlumab was being developed by Janssen Biotech prior to discontinuation in 2012[13] due to limited success in clinical trials.

References
  1. Pienta KJ, Machiels JP, Schrijvers D, Alekseev B, Shkolnik M, Crabb SJ, et al. (June 2013). "Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer". Investigational New Drugs. 31 (3): 760–8. doi:10.1007/s10637-012-9869-8. PMID 22907596. S2CID 29365102.
  2. "CNTO-888/Carlumab" (PDF). Janssen (J&J). Archived from the original (PDF) on 2017-01-31. Retrieved 2017-03-24.
  3. "Carlumab". NCI Drug Dictionary. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute (NCI). 2011-02-02. Retrieved 2017-03-24.
  4. Fetterly GJ, Aras U, Meholick PD, Takimoto C, Seetharam S, McIntosh T, et al. (October 2013). "Utilizing pharmacokinetics/pharmacodynamics modeling to simultaneously examine free CCL2, total CCL2 and carlumab (CNTO 888) concentration time data". Journal of Clinical Pharmacology. 53 (10): 1020–7. doi:10.1002/jcph.140. PMID 23878055.
  5. Obmolova G, Teplyakov A, Malia TJ, Grygiel TL, Sweet R, Snyder LA, Gilliland GL (June 2012). "Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO 888". Molecular Immunology. 51 (2): 227–33. doi:10.1016/j.molimm.2012.03.022. PMID 22487721.
  6. "Statement On A Nonproprietary Name Adopted By The USAN Council: Carlumab" (PDF). American Medical Association.
  7. World Health Organization (2010). "Proposed International Nonproprietary Names: List 104" (PDF). WHO Drug Information. 24 (4). Geneva: World Health Organization. p. 361. ISSN 1010-9609. Retrieved 17 August 2015.
  8. Raghu G, Martinez FJ, Brown KK, Costabel U, Cottin V, Wells AU, et al. (December 2015). "CC-chemokine ligand 2 inhibition in idiopathic pulmonary fibrosis: a phase 2 trial of carlumab". The European Respiratory Journal. 46 (6): 1740–50. doi:10.1183/13993003.01558-2014. PMID 26493793.
  9. Clinical trial number NCT00786201 for "A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF)" at ClinicalTrials.gov
  10. Clinical trial number NCT00992186 for "A Study of the Safety and Efficacy of Single-agent Carlumab (an Anti-Chemokine Ligand 2 [CCL2]) in Participants With Metastatic Castrate-Resistant Prostate Cancer" at ClinicalTrials.gov
  11. Sandhu SK, Papadopoulos K, Fong PC, Patnaik A, Messiou C, Olmos D, et al. (April 2013). "A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors". Cancer Chemotherapy and Pharmacology. 71 (4): 1041–50. doi:10.1007/s00280-013-2099-8. PMID 23385782. S2CID 23586468.
  12. Clinical trial number NCT00537368 for "First Study of the Safety of CNTO 888 in Patients With Solid Tumors" at ClinicalTrials.gov
  13. "Annual Report 2012: Research and Development". MorphoSys. 2012. Retrieved 2017-03-24.
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