Carlumab

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Carlumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetMCP-1
Clinical data
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
KEGG
Chemical and physical data
FormulaC6442H9966N1706O2018S40
Molar mass144.88 kg/mol 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

  1. ^ a b Pienta, Kenneth J.; Machiels, Jean-Pascal; Schrijvers, Dirk; Alekseev, Boris; Shkolnik, Mikhail; Crabb, Simon J.; Li, Susan; Seetharam, Shobha; Puchalski, Thomas A. (2013-06-01). "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): 760–768. doi:10.1007/s10637-012-9869-8. ISSN 1573-0646. PMID 22907596.
  2. ^ a b c "Janssen 2014 Compound Information CNT0888" (PDF).
  3. ^ a b "NCI Drug Dictionary". National Cancer Institute. 2011-02-02. Retrieved 2017-03-24.
  4. ^ Fetterly, Gerald J.; Aras, Urvi; Meholick, Patricia D.; Takimoto, Chris; Seetharam, Shobha; McIntosh, Thomas; de Bono, Johann S.; Sandhu, Shahneen K.; Tolcher, Anthony (2013-10-01). "Utilizing pharmacokinetics/pharmacodynamics modeling to simultaneously examine free CCL2, total CCL2 and carlumab (CNTO 888) concentration time data". The Journal of Clinical Pharmacology. 53 (10): 1020–1027. doi:10.1002/jcph.140. ISSN 1552-4604. PMID 23878055.
  5. ^ Obmolova, Galina; Teplyakov, Alexey; Malia, Thomas J.; Grygiel, Tami L. R.; Sweet, Raymond; Snyder, Linda A.; Gilliland, Gary L. (2012-06-01). "Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO 888". Molecular Immunology. 51 (2): 227–233. doi:10.1016/j.molimm.2012.03.022. ISSN 1872-9142. 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. ^ "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". www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A3376. American Thoracic Society International Conference Abstracts. American Thoracic Society. May 2013. pp. A3376. doi:10.1164/ajrccm-conference.2013.187.1_meetingabstracts.a3376 (inactive 2019-08-20).{{cite book}}: CS1 maint: DOI inactive as of August 2019 (link)
  9. ^ "A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF) - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2017-03-24.
  10. ^ "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 - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2017-03-24.
  11. ^ Sandhu, Shahneen K.; Papadopoulos, Kyri; Fong, Peter C.; Patnaik, Amita; Messiou, Christina; Olmos, David; Wang, George; Tromp, Brenda J.; Puchalski, Thomas A. (2013-04-01). "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): 1041–1050. doi:10.1007/s00280-013-2099-8. ISSN 1432-0843. PMID 23385782.
  12. ^ "First Study of the Safety of CNTO 888 in Patients With Solid Tumors - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2017-03-24.
  13. ^ "Research and Development | MorphoSys 2012". reports.morphosys.com. Retrieved 2017-03-24.


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