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Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment

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Title
Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment
Author(s)
Jin-Sung Park; Kim I.-K.; Sangyeul Han; Intae Park; Kim C.; Jeomil Bae; Oh S.J.; Lee S.; Kim J.H.; Woo D.-C.; He Y.; Augustin H.G.; Kim I.; Lee D.; Gou Young Koh
Publication Date
2016-12
Journal
CANCER CELL, v.30, no.6, pp.953 - 967
Publisher
CELL PRESS
Abstract
A destabilized tumor vasculature leads to limited drug delivery, hypoxia, detrimental tumor microenvironment, and even metastasis. We performed a side-by-side comparison of ABTAA (Ang2-Binding and Tie2-Activating Antibody) and ABA (Ang2-Blocking Antibody) in mice with orthotopically implanted glioma, with subcutaneously implanted Lewis lung carcinoma, and with spontaneous mammary cancer. We found that Tie2 activation induced tumor vascular normalization, leading to enhanced blood perfusion and chemotherapeutic drug delivery, markedly lessened lactate acidosis, and reduced tumor growth and metastasis. Moreover, ABTAA favorably altered the immune cell profile within tumors. Together, our findings establish that simultaneous Tie2 activation and Ang2 inhibition form a powerful therapeutic strategy to elicit a favorable tumor microenvironment and enhanced delivery of a chemotherapeutic agent into tumors. © 2016 Elsevier Inc
URI
https://pr.ibs.re.kr/handle/8788114/3339
ISSN
1535-6108
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
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