Oncotarget

Research Papers:

Targeting endosialin/CD248 through antibody-mediated internalization results in impaired pericyte maturation and dysfunctional tumor microvasculature

Katherine Rybinski, Hongxia Z. Imtiyaz, Barrie Mittica, Brian Drozdowski, James Fulmer, Keiji Furuuchi, Shawn Fernando, Marianne Henry, Qimin Chao, Brad Kline, Earl Albone, Jason Wustner, JianMin Lin, Nicholas C. Nicolaides, Luigi Grasso, Yuhong Zhou _

PDF |  HTML  |  Supplementary Files  |  Author Information  |  Order a Reprint

Oncotarget. 2015; 6:25429-25440. doi: 10.18632/oncotarget.4559

Metrics: PDF 464 views  |   HTML 163 views  |   ?  


Abstract

Katherine Rybinski1, Hongxia Z. Imtiyaz1, Barrie Mittica1, Brian Drozdowski1, James Fulmer1, Keiji Furuuchi1, Shawn Fernando1, Marianne Henry1, Qimin Chao1, Brad Kline1, Earl Albone1, Jason Wustner1, JianMin Lin1, Nicholas C. Nicolaides1, Luigi Grasso1, Yuhong Zhou1

1Morphotek, Inc., Exton, PA 19341, USA

Correspondence to:

Yuhong Zhou, e-mail: zhou@morphotek.com

Keywords: endosialin, CD248, MORAb-004, tumor microvasculature, α-SMA

Received: May 11, 2015     Accepted: June 22, 2015     Published: July 04, 2015

ABSTRACT

Over-expression of endosialin/CD248 (herein referred to as CD248) has been associated with increased tumor microvasculature in various tissue origins which makes it an attractive anti-angiogenic target. In an effort to target CD248, we have generated a human CD248 knock-in mouse line and MORAb-004, the humanized version of the mouse anti-human CD248 antibody Fb5. Here, we report that MORAb-004 treatment significantly impacted syngeneic tumor growth and tumor metastasis in the human CD248 knock-in mice. In comparison with untreated tumors, MORAb-004 treated tumors displayed overall shortened and distorted blood vessels. Immunofluorescent staining of tumor sections revealed drastically more small and dysfunctional vessels in the treated tumors. The CD248 levels on cell surfaces of neovasculature pericytes were significantly reduced due to its internalization. This reduction of CD248 was also accompanied by reduced α-SMA expression, depolarization of pericytes and endothelium, and ultimately dysfunctional microvessels. These results suggest that MORAb-004 reduced CD248 on pericytes, impaired tumor microvasculature maturation and ultimately suppressed tumor development.

Author Information

Katherine Rybinski

Hongxia Z. Imtiyaz

Barrie Mittica

Brian Drozdowski

James Fulmer

Keiji Furuuchi

Shawn Fernando

Marianne Henry

Qimin Chao

Brad Kline

Earl Albone

Jason Wustner

JianMin Lin

Nicholas C. Nicolaides

Luigi Grasso

Yuhong Zhou
Primary Contact  _


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 4559