Carlumab Explained

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.

The inhibitory binding of Carlumab to CCL2 was hypothesized to inhibit angiogenesis and consequently modulate tumor cell proliferation. 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] castration-resistant metastatic prostate cancer^[1] and solid tumors.^[9]

Carlumab was being developed by Janssen Biotech prior to discontinuation in 2012^[10] due to limited success in clinical trials.

Notes and References

1. Pienta KJ, Machiels JP, Schrijvers D, Alekseev B, Shkolnik M, Crabb SJ, Li S, Seetharam S, Puchalski TA, Takimoto C, Elsayed Y, Dawkins F, de Bono JS . 6 . 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 . June 2013 . 22907596 . 10.1007/s10637-012-9869-8 . 29365102 .
2. Web site: CNTO-888/Carlumab . Janssen (J&J) . 2017-03-24 . https://web.archive.org/web/20170131063833/https://ncats.nih.gov/files/CNTO-888.pdf . 2017-01-31 . dead .
3. Web site: Carlumab . NCI Drug Dictionary . U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute (NCI) . 2017-03-24. 2011-02-02.
4. Fetterly GJ, Aras U, Meholick PD, Takimoto C, Seetharam S, McIntosh T, de Bono JS, Sandhu SK, Tolcher A, Davis HM, Zhou H, Puchalski TA . 6 . 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 . October 2013 . 23878055 . 10.1002/jcph.140 . 10638060 .
5. Obmolova G, Teplyakov A, Malia TJ, Grygiel TL, Sweet R, Snyder LA, Gilliland GL . Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO 888 . Molecular Immunology . 51 . 2 . 227–33 . June 2012 . 22487721 . 10.1016/j.molimm.2012.03.022 .
6. Web site: Statement On A Nonproprietary Name Adopted By The USAN Council: Carlumab. American Medical Association.
7. News: Proposed International Nonproprietary Names: List 104. World Health Organization. 2010. 17 August 2015. World Health Organization. 4. Geneva. 24. 361. 1010-9609. WHO Drug Information.
8. Raghu G, Martinez FJ, Brown KK, Costabel U, Cottin V, Wells AU, Lancaster L, Gibson KF, Haddad T, Agarwal P, Mack M, Dasgupta B, Nnane IP, Flavin SK, Barnathan ES . 6 . CC-chemokine ligand 2 inhibition in idiopathic pulmonary fibrosis: a phase 2 trial of carlumab . The European Respiratory Journal . 46 . 6 . 1740–50 . December 2015 . 26493793 . 10.1183/13993003.01558-2014 . free .
9. Sandhu SK, Papadopoulos K, Fong PC, Patnaik A, Messiou C, Olmos D, Wang G, Tromp BJ, Puchalski TA, Balkwill F, Berns B, Seetharam S, de Bono JS, Tolcher AW . 6 . 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 . April 2013 . 23385782 . 10.1007/s00280-013-2099-8 . 23586468 .
10. Web site: Annual Report 2012: Research and Development . MorphoSys . 2012 . 2017-03-24.