The dual effects of a novel peptibody on angiogenesis inhibition and M2 macrophage polarization on sarcoma

Cancer Letters
Xiaoqing ZhuYuanming Qi

Abstract

Inhibition of the VEGF/VEGF receptor (VEGFR) and angiopoietin-2 (Ang-2)/TEK receptor tyrosine kinase (Tie-2) pathway is a potential target for tumor angiogenesis. We previously showed that a peptide AS16 which dually inhibits VEGFR/Ang-2 could reduce the tumor growth and decrease the number of microvessels in tumor. However, its short circulating half-life in the serum limits its clinical applications. In this study, as an effort to prolong the short in vivo half-life of AS16, we designed a fusion protein containing peptide AS16 and an IgG Fc fragment. Pharmacokinetic study also revealed that AS16-Fc has a prolonged circulating half-life of about 231 min in rats. We examined the effects of treatment on the tumor vasculature and immune cell populations, tumor growth, in both the MCA-205 and S180 tumor models. We found that AS16-Fc dramatically reduced tumor volume, vascular density and tumor-associated macrophages. Macrophages were identified as potential novel targets following anti-angiogenic therapy, our findings imply a novel role for anti-angiogenic peptide AS16-Fc. These findings indicate that AS16-Fc could be more effective on inhibiting tumor growth angiogenesis and tumor immune microenvironment than that of peptide AS16.

Citations

Feb 8, 2018·Frontiers in Oncology·Taku FujimuraSetsuya Aiba
Oct 24, 2018·Frontiers in Immunology·Emile J ClappaertDamya Laoui
Feb 3, 2021·Journal for Immunotherapy of Cancer·Harsimrat Kaur BirdiMichele Ardolino
Mar 31, 2021·Cancer Metastasis Reviews·Victor Delprat, Carine Michiels
Oct 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Si-Yu ZhangWei-Bing Yang
Jun 22, 2018·Case Reports in Oncology·Kana TakedaSetsuya Aiba

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