HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo.

Abstract
Integrins of the alphav family, such as alphavbeta3 and alphavbeta5, are implicated in tumor-induced angiogenesis; but their role in tumor growth has not been fully explored. CNTO 95 is a fully human antibody that recognizes the alphav family of integrins and is likely to be less immunogenic in humans compared to chimeric or humanized antibodies. CNTO 95 bound to purified alphavbeta3 and alphavbeta5 with a Kd of approximately 200 pM and to alphav integrin-expressing human cells with a Kd of 1-24 nM. In vitro, CNTO 95 inhibited human melanoma cell adhesion, migration and invasion at doses ranging 7-20 nM. In a rat aortic ring sprouting assay, CNTO 95 (approx. 70 nM) completely inhibited sprouting. Using a human melanoma xenograft model in nude mice wherein CNTO 95 recognized alphavbeta3 and alphavbeta5 on human tumor cells but not mouse angiogenic integrins, CNTO 95 (10 mg/kg, 3 times/week) inhibited growth of human melanoma tumors in nude mice by approximately 80% (p = 0.0005), suggesting that CNTO 95 inhibited human tumor growth independently of its antiangiogenic activity. In a nude rat human xenograft model where CNTO 95 binds and blocks both tumor and host integrins, this antibody (10 mg/kg once/week) reduced final tumor weight by >99% (p < 0.0001). Based on these preclinical data, a dose-escalating phase I clinical trial in cancer patients has been initiated. To our knowledge, CNTO 95 is the first fully human MAb to alphav integrins that has potent antitumor and antiangiogenic properties in in vivo preclinical models.
AuthorsMohit Trikha, Zhao Zhou, Jeffrey A Nemeth, Qiming Chen, Celia Sharp, Eva Emmell, Jill Giles-Komar, Marian T Nakada
JournalInternational journal of cancer (Int J Cancer) Vol. 110 Issue 3 Pg. 326-35 (Jun 20 2004) ISSN: 0020-7136 [Print] United States
PMID15095296 (Publication Type: Journal Article)
CopyrightCopyright 2004 Wiley-Liss, Inc.
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Drug Combinations
  • Integrin alphaV
  • Integrin alphaVbeta3
  • Integrins
  • Laminin
  • Proteoglycans
  • Receptors, Vitronectin
  • integrin alphaVbeta5
  • Fibroblast Growth Factor 2
  • matrigel
  • Collagen
  • intetumumab
Topics
  • Animals
  • Antibodies, Monoclonal (chemistry, pharmacology, therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Antibody Affinity
  • Antibody Specificity
  • Antineoplastic Agents (pharmacology)
  • Aorta (metabolism, pathology)
  • Blotting, Western
  • Cattle
  • Cell Adhesion
  • Cell Division
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cells, Cultured
  • Collagen (pharmacology)
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Endothelium, Vascular (cytology)
  • Fibroblast Growth Factor 2 (metabolism)
  • Haplorhini
  • Humans
  • Integrin alphaV (chemistry)
  • Integrin alphaVbeta3 (metabolism)
  • Integrins (metabolism)
  • Kinetics
  • Laminin (pharmacology)
  • Macaca fascicularis
  • Melanoma (immunology, therapy)
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Placenta (metabolism, pathology)
  • Protein Binding
  • Proteoglycans (pharmacology)
  • Rats
  • Rats, Nude
  • Receptors, Vitronectin (metabolism)
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: