Carlumab

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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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]

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

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  1. ^ a b 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. ^ a b c "CNTO-888/Carlumab" (PDF). Janssen (J&J). Archived from the original (PDF) on 2017-01-31. Retrieved 2017-03-24.
  3. ^ a b "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. S2CID 10638060.
  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. Vol. 24, no. 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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