TY  - JOUR
AU  - Park, Jin-Sung
AU  - Kim, Il-Kug
AU  - Han, Sangyeul
AU  - Park, Intae
AU  - Kim, Chan
AU  - Bae, Jeomil
AU  - Oh, Seung Ja
AU  - Lee, Seungjoo
AU  - Kim, Jeong Hoon
AU  - Woo, Dong-Cheol
AU  - He, Yulong
AU  - Augustin, Hellmut
AU  - Kim, Injune
AU  - Lee, Doheon
AU  - Koh, Gou Young
TI  - Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment.
JO  - Cancer cell
VL  - 30
IS  - 6
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2017-05377
SP  - 953 - 967
PY  - 2016
AB  - 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.
KW  - Antibodies (NLM Chemicals)
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Dacarbazine (NLM Chemicals)
KW  - Receptor, TIE-2 (NLM Chemicals)
KW  - Tek protein, mouse (NLM Chemicals)
KW  - Ang2 protein, mouse (NLM Chemicals)
KW  - Ribonuclease, Pancreatic (NLM Chemicals)
KW  - temozolomide (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27960088
DO  - DOI:10.1016/j.ccell.2016.10.018
UR  - https://inrepo02.dkfz.de/record/130298
ER  -