Normalization of tumor vasculature by Tie2 activating antibody enhances drug delivery and reduces tumor growth and metastasis

Abstract

A tumor vasculature which are destabilized in structure and function leads to limited drug delivery, hypoxia, unfavorable tumor microenvironment, and even metastasis. I performed a side-by-side comparison of ABTAA (Ang2-Binding and Tie2-Activating Antibody) and ABA (Ang2-Blocking Antibody) in mice with subcutaneously implanted Lewis lung carcinoma, and with spontaneous mammary cancer. I found that Tie2 activation-induced tumor vascular normalization, leading to enhanced blood perfusion and chemotherapeutic drug delivery, and reduced tumor growth and metastasis. Moreover, ABTAA favorably altered the immune cell profile within tumors. Together, my findings establish that simultaneous Tie2 activation and Ang2 inhibition form a powerful therapeutic strategy to elicit a favorable tumor microenvironment and enhanced delivery of chemotherapeutic agent into tumors.