| Autor: |
Shen J; ImClone Systems Incorporated, New York, NY 10014, USA. juqun.shen@imclone.com, Vil MD, Zhang H, Tonra JR, Rong LL, Damoci C, Prewett M, Deevi DS, Kearney J, Surguladze D, Jimenez X, Iacolina M, Bassi R, Zhou K, Balderes P, Mangalampalli VR, Loizos N, Ludwig DL, Zhu Z |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2007 Jun 15; Vol. 357 (4), pp. 1142-7. Date of Electronic Publication: 2007 Apr 19. |
| DOI: |
10.1016/j.bbrc.2007.04.075 |
| Abstrakt: |
Platelet-derived growth factor (PDGF) and its receptors (PDGFR) play important roles in tumorigenesis through stimulating tumor growth and promoting angiogenesis via enhancing pericyte recruitment and vessel maturation. Here we produced a neutralizing antibody, 1B3, directed against mouse PDGFRbeta. 1B3 binds to PDGFRbeta with high affinity (9x10(-11)M) and blocks PDGF-BB from binding to the receptor with an IC(50) of approximately 1.2 nM. The antibody also blocks ligand-stimulated activation of PDGFRbeta and downstream signaling molecules, including Akt and MAPK p42/44, in tumor cells. In animal studies, 1B3 significantly enhanced the antitumor and the anti-angiogenic activities of DC101, an antibody directed against mouse vascular endothelial growth factor receptor 2, in a pancreatic (BxPC-3) and a non-small cell lung (NCI-H460) tumor xenograft models. Treatment with the combination of 1B3 and DC101 in BxPC-3 xenograft-bearing mice resulted in tumor regression in 58% of mice compared to that in 18% of mice treated with DC101 alone. Taken together, these results lend great support to use PDGFRbeta antagonists in combinations with other antitumor and/or anti-angiogenic agents in the treatment of a variety of cancers. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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