Vascular endothelial-targeted therapy combined with cytotoxic chemotherapy induces inflammatory intratumoral infiltrates and inhibits tumor relapses after surgery.

Neoplasia : an International Journal for Oncology Research
Brendan F JudySunil Singhal

Abstract

Surgery is the most effective therapy for cancer in the United States, but disease still recurs in more than 40% of patients within 5 years after resection. Chemotherapy is given postoperatively to prevent relapses; however, this approach has had marginal success. After surgery, recurrent tumors depend on rapid neovascular proliferation to deliver nutrients and oxygen. Phosphatidylserine (PS) is exposed on the vascular endothelial cells in the tumor microenvironment but is notably absent on blood vessels in normal tissues. Thus, PS is an attractive target for cancer therapy after surgery. Syngeneic mice bearing TC1 lung cancer tumors were treated with mch1N11 (a novel mouse chimeric monoclonal antibody that targets PS), cisplatin (cis), or combination after surgery. Tumor relapses and disease progression were decreased 90% by combination therapy compared with a 50% response rate for cis alone (P = .02). Mice receiving postoperative mch1N11 had no wound-related complications or added systemic toxicity in comparison to control animals. Mechanistic studies demonstrated that the effects of mch1N11 were associated with a dense infiltration of inflammatory cells, particularly granulocytes. This strategy was independent of the adaptiv...Continue Reading

Citations

Dec 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jarrod PredinaSunil Singhal
Aug 1, 2015·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Jane J KeatingSunil Singhal
Oct 23, 2015·International Journal of Molecular Imaging·Elizabeth De JesusSunil Singhal
May 13, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Jarrod D PredinaSunil Singhal
Aug 31, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brian MadajewskiSunil Singhal
Jun 10, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kombo F N'GuessanXiaoyang Qi
Nov 30, 2018·Chemical Reviews·Bernhard EnglingerWalter Berger

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