alexa Selective Activity Against Proliferating Tumor Endothelial Cells by CVX-2 A Thrombospondin-1 Mimetic CovX-Body (TM).
Immunology

Immunology

Immunotherapy: Open Access

Author(s): Julia Coronella, Lingna Li, Kimberly Johnson, Steven PirieShepherd, Robert Murphy

Abstract Share this page

CVX-22 is a CovX-BodyTM , produced by covalently attaching a Thrombospondin-1 (TSP1) type 1 repeat peptide mimetic to the Fab binding site of a humanized IgG1 molecule. CVX-22 has markedly increased serum stability in comparison with the native TSP1 type 1 repeat peptide mimetic. CVX-22 significantly decreased tumor growth and microvessel density in the syngeneic B16 and xenograft C32 mouse models of melanoma, consistent with its previously described antiangiogenic activity. To further dissect the mechanism of this effect, the numbers and proliferation status of defined tumor endothelial cell (TEC) subsets from the B16 model were examined by flow cytometry and immunohistochemistry. Overall proliferation of TEC was reduced by treatment with CVX-22, as measured by an 82% decrease in BrdU labeling. This reduced proliferation resulted from the selective reduction in numbers of a specific subset of cells, the actively proliferating VEGFR2-positive subpopulation. In contrast, the numbers of VEGFR2-negative TEC remained unchanged. Because the VEGFR2-positive subset of TEC actively propagates, while the VEGFR2-negative subset is quiescent, a reduction in numbers of the active compartment significantly reduces the overall number of labeled TEC. However, while the numbers of active VEGFR2-positive TEC were reduced, the VEGFR2-positive subset remained qualitatively unchanged. The proliferation rate and VEGFR2 receptor density of this VEGFR2-positive subpopulation was unaffected, indicating that the selective reduction in numbers of activated TEC occurred by attrition rather than induction of quiescence. Increased caspase staining of TEC in CVX-22-treated tumors suggested induction of apoptosis in vivo. These data indicate that CVX-22 acts as an antiangiogenic by selective removal of only the most mitotically active, VEGFR2-positive TEC. The overrepresentation of this subpopulation of cells in sites of tumor angiogenesis may confer a unique specificity for tumor vasculature by CVX-22.
  • To read the full article Visit
  • Subscription
This article was published in Anticancer Research and referenced in Immunotherapy: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

agrifoodaquavet@omicsonline.com

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

clinical_biochem@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

chemicaleng_chemistry@omicsonline.com

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

environmentalsci@omicsonline.com

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

engineering@omicsonline.com

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

generalsci_healthcare@omicsonline.com

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

genetics_molbio@omicsonline.com

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immuno_microbio@omicsonline.com

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

omics@omicsonline.com

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

mathematics_physics@omicsonline.com

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

medical@omicsonline.com

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuro_psychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

pharma@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version