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| {{Drugbox | | {{Short description|Human monoclonal antibody for the treatment of inflammatory diseases}} |
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| | verifiedrevid = 460019588
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| | type = mab
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| | image =
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| | alt =
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| | mab_type = mab
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| | source = u
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| | target = [[MCP-1]]
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| | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
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| | pregnancy_US = <!-- A / B / C / D / X -->
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| | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
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| | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
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| | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
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| | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
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| | CAS_number_Ref = {{cascite|changed|??}}
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| | CAS_number = 915404-94-3
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| | ATC_prefix = none
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| | KEGG_Ref = {{keggcite|changed|kegg}}
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| | KEGG = D09877
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| | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
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| | ChemSpiderID = none
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| | C=6442 | H=9966 | N=1706 | O=2018 | S=40
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| | molecular_weight = 144.88 kg/mol
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| '''Carlumab''' (alternate identifier CNTO 888<ref name="Pienta 760–768">{{Cite journal|last=Pienta|first=Kenneth J.|last2=Machiels|first2=Jean-Pascal|last3=Schrijvers|first3=Dirk|last4=Alekseev|first4=Boris|last5=Shkolnik|first5=Mikhail|last6=Crabb|first6=Simon J.|last7=Li|first7=Susan|last8=Seetharam|first8=Shobha|last9=Puchalski|first9=Thomas A.|date=2013-06-01|title=Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer|journal=Investigational New Drugs|volume=31|issue=3|pages=760–768|doi=10.1007/s10637-012-9869-8|issn=1573-0646|pmid=22907596}}</ref>) is a discontinued human [[Monoclonal antibody|recombinant monoclonal antibody]] (type IgG1 kappa)<ref name=":0">{{Cite web|url=https://ncats.nih.gov/files/CNTO-888.pdf|title=Janssen 2014 Compound Information CNT0888|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> that targets human [[CCL2|CC chemokine ligand 2]] (CCL2)/monocyte chemoattractant protein ([[MCP-1|MCP1]]).<ref name=":1">{{Cite web|url=https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=573742|title=NCI Drug Dictionary|website=National Cancer Institute|language=en|access-date=2017-03-24|date=2011-02-02}}</ref><ref>{{Cite journal|last=Fetterly|first=Gerald J.|last2=Aras|first2=Urvi|last3=Meholick|first3=Patricia D.|last4=Takimoto|first4=Chris|last5=Seetharam|first5=Shobha|last6=McIntosh|first6=Thomas|last7=de Bono|first7=Johann S.|last8=Sandhu|first8=Shahneen K.|last9=Tolcher|first9=Anthony|date=2013-10-01|title=Utilizing pharmacokinetics/pharmacodynamics modeling to simultaneously examine free CCL2, total CCL2 and carlumab (CNTO 888) concentration time data|journal=The Journal of Clinical Pharmacology|language=en|volume=53|issue=10|pages=1020–1027|doi=10.1002/jcph.140|pmid=23878055|issn=1552-4604}}</ref><ref>{{Cite journal|last=Obmolova|first=Galina|last2=Teplyakov|first2=Alexey|last3=Malia|first3=Thomas J.|last4=Grygiel|first4=Tami L. R.|last5=Sweet|first5=Raymond|last6=Snyder|first6=Linda A.|last7=Gilliland|first7=Gary L.|date=2012-06-01|title=Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO 888|journal=Molecular Immunology|volume=51|issue=2|pages=227–233|doi=10.1016/j.molimm.2012.03.022|issn=1872-9142|pmid=22487721}}</ref> Carlumab was under development for use in the treatment of oncology and immune indications<ref>{{cite web|url=http://www.ama-assn.org/resources/doc/usan/carlumab.pdf|title=Statement On A Nonproprietary Name Adopted By The USAN Council: Carlumab|publisher=[[American Medical Association]]}}</ref><ref>{{Cite news|url=http://www.who.int/medicines/publications/druginformation/innlists/PL104.pdf|title=Proposed International Nonproprietary Names: List 104|last=World Health Organization|date=2010|work=|access-date=17 August 2015|publisher=World Health Organization|issue=4|location=Geneva|volume=24|page=361|issn=1010-9609|newspaper=[[WHO Drug Information]]}}</ref> and was studied for application in [[Systemic scleroderma|systemic sclerosis]], [[atherosclerosis]], [[diabetic nephropathy]], [[liver fibrosis]] and [[Diabetes|type 2 diabetes]].<ref name=":0" /> | | '''Carlumab''' is a [[human monoclonal antibody]] that was developed for the treatment of various [[inflammatory diseases]]. It specifically targets and binds to the [[chemokine]] known as [[CCL2]] (chemokine (C-C motif) ligand 2), also referred to as [[monocyte chemoattractant protein-1]] (MCP-1). This chemokine plays a significant role in the recruitment of [[monocytes]], [[memory T cells]], and [[dendritic cells]] to sites of inflammation. |
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| The inhibitory binding of Carlumab to CCL2 was hypothesized to inhibit [[angiogenesis]] and consequently modulate tumor cell proliferation.<ref name=":1" /><ref name=":0" /> 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 trial]]s evaluating the efficacy, safety and dose requirements of the drug. Clinical trials for Carlumab include studies of idiopathic [[pulmonary fibrosis]],<ref>{{Cite book|title=www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A3376|pages=A3376|chapter-url=http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A3376|doi=10.1164/ajrccm-conference.2013.187.1_meetingabstracts.a3376|chapter=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|publisher=American Thoracic Society|date=May 2013|series=American Thoracic Society International Conference Abstracts|doi-broken-date=2019-08-20}}</ref><ref>{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT00786201?term=CNTO-888&rank=1|title=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|website=clinicaltrials.gov|language=en|access-date=2017-03-24}}</ref> castration-resistant metastatic [[prostate cancer]]<ref name="Pienta 760–768"/><ref>{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT00992186?term=CNTO-888&rank=4|title=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|website=clinicaltrials.gov|language=en|access-date=2017-03-24}}</ref> and solid tumors.<ref>{{Cite journal|last=Sandhu|first=Shahneen K.|last2=Papadopoulos|first2=Kyri|last3=Fong|first3=Peter C.|last4=Patnaik|first4=Amita|last5=Messiou|first5=Christina|last6=Olmos|first6=David|last7=Wang|first7=George|last8=Tromp|first8=Brenda J.|last9=Puchalski|first9=Thomas A.|date=2013-04-01|title=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|journal=Cancer Chemotherapy and Pharmacology|volume=71|issue=4|pages=1041–1050|doi=10.1007/s00280-013-2099-8|issn=1432-0843|pmid=23385782}}</ref><ref>{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT00537368?term=CNTO-888&rank=3|title=First Study of the Safety of CNTO 888 in Patients With Solid Tumors - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|language=en|access-date=2017-03-24}}</ref>
| | ==Mechanism of Action== |
| | Carlumab functions by inhibiting the activity of CCL2. By binding to CCL2, carlumab prevents this chemokine from interacting with its receptor, [[CCR2]] (C-C chemokine receptor type 2), on the surface of target cells. This blockade reduces the migration of inflammatory cells to the site of inflammation, thereby potentially reducing the inflammatory response. |
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| Carlumab was being developed by Janssen Biotech prior to discontinuation in 2012<ref>{{Cite web|url=http://reports.morphosys.com/2012/group-management-report/research-and-development|title=Research and Development {{!}} MorphoSys 2012|website=reports.morphosys.com|access-date=2017-03-24}}</ref> due to limited success in clinical trials. | | ==Development and Clinical Trials== |
| | Carlumab was developed by [[Centocor]], a biotechnology company that focuses on the development of monoclonal antibodies. The drug underwent several phases of clinical trials to evaluate its safety and efficacy in treating conditions such as [[rheumatoid arthritis]], [[asthma]], and [[cancer]]. |
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| == References == | | ===Rheumatoid Arthritis=== |
| <references/>
| | In clinical trials for [[rheumatoid arthritis]], carlumab was tested for its ability to reduce the symptoms of this chronic inflammatory disorder. However, the results did not demonstrate significant efficacy compared to existing treatments, leading to a discontinuation of its development for this indication. |
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| {{Monoclonals for immune system}}
| | ===Asthma=== |
| {{Chemokine receptor modulators}}
| | Carlumab was also evaluated in patients with [[asthma]], particularly those with severe, uncontrolled asthma. The trials aimed to assess whether blocking CCL2 could reduce airway inflammation and improve lung function. Despite initial hopes, the outcomes did not show a substantial benefit over standard therapies. |
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| [[Category:Johnson & Johnson]] | | ===Cancer=== |
| | The role of CCL2 in [[tumor]] progression and metastasis prompted investigations into carlumab as a potential [[anticancer]] therapy. The hypothesis was that by inhibiting CCL2, carlumab could reduce the recruitment of tumor-associated macrophages, which are known to support tumor growth and spread. However, clinical trials did not yield promising results, and development for cancer treatment was not pursued further. |
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| | ==Challenges and Discontinuation== |
| | Despite the theoretical benefits of targeting CCL2, carlumab faced several challenges in clinical development. The redundancy and complexity of the [[chemokine]] network in humans meant that blocking a single chemokine like CCL2 did not produce the expected therapeutic effects. Additionally, the body’s ability to compensate for the blockade by upregulating other chemokines or pathways limited the efficacy of carlumab. |
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| {{monoclonal-antibody-stub}}
| | As a result of these challenges, the development of carlumab was eventually discontinued, and it is not currently available as a treatment option. |
| {{antineoplastic-drug-stub}}
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| {{dictionary-stub1}}
| | ==Related Pages== |
| | * [[Monoclonal antibody]] |
| | * [[Chemokine]] |
| | * [[Rheumatoid arthritis]] |
| | * [[Asthma]] |
| | * [[Cancer]] |
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| | [[Category:Monoclonal antibodies]] |
| | [[Category:Immunology]] |
| | [[Category:Inflammatory diseases]] |
Human monoclonal antibody for the treatment of inflammatory diseases
Carlumab is a human monoclonal antibody that was developed for the treatment of various inflammatory diseases. It specifically targets and binds to the chemokine known as CCL2 (chemokine (C-C motif) ligand 2), also referred to as monocyte chemoattractant protein-1 (MCP-1). This chemokine plays a significant role in the recruitment of monocytes, memory T cells, and dendritic cells to sites of inflammation.
Mechanism of Action[edit]
Carlumab functions by inhibiting the activity of CCL2. By binding to CCL2, carlumab prevents this chemokine from interacting with its receptor, CCR2 (C-C chemokine receptor type 2), on the surface of target cells. This blockade reduces the migration of inflammatory cells to the site of inflammation, thereby potentially reducing the inflammatory response.
Development and Clinical Trials[edit]
Carlumab was developed by Centocor, a biotechnology company that focuses on the development of monoclonal antibodies. The drug underwent several phases of clinical trials to evaluate its safety and efficacy in treating conditions such as rheumatoid arthritis, asthma, and cancer.
Rheumatoid Arthritis[edit]
In clinical trials for rheumatoid arthritis, carlumab was tested for its ability to reduce the symptoms of this chronic inflammatory disorder. However, the results did not demonstrate significant efficacy compared to existing treatments, leading to a discontinuation of its development for this indication.
Carlumab was also evaluated in patients with asthma, particularly those with severe, uncontrolled asthma. The trials aimed to assess whether blocking CCL2 could reduce airway inflammation and improve lung function. Despite initial hopes, the outcomes did not show a substantial benefit over standard therapies.
The role of CCL2 in tumor progression and metastasis prompted investigations into carlumab as a potential anticancer therapy. The hypothesis was that by inhibiting CCL2, carlumab could reduce the recruitment of tumor-associated macrophages, which are known to support tumor growth and spread. However, clinical trials did not yield promising results, and development for cancer treatment was not pursued further.
Challenges and Discontinuation[edit]
Despite the theoretical benefits of targeting CCL2, carlumab faced several challenges in clinical development. The redundancy and complexity of the chemokine network in humans meant that blocking a single chemokine like CCL2 did not produce the expected therapeutic effects. Additionally, the body’s ability to compensate for the blockade by upregulating other chemokines or pathways limited the efficacy of carlumab.
As a result of these challenges, the development of carlumab was eventually discontinued, and it is not currently available as a treatment option.
Related Pages[edit]
