Immunotoxin targeting CD133(+) breast carcinoma cells

Drug Delivery and Translational Research
John R OhlfestDaniel A Vallera

Abstract

CD133 expression enriches for tumor-initiating cells and is a negative prognostic factor in numerous cancers. We previously developed an immunotoxin against CD133 by fusing a gene fragment encoding the scFv portion of an anti-CD133 antibody to a gene fragment encoding deimmunized PE38KDEL. The resulting fusion protein, dCD133KDEL, demonstrated potent antitumor activity following intratumoral delivery into head neck cell carcinoma xenografts. However, the efficacy against other tumors and the tolerability of systemic administration remained unclear. The purpose of this study was to evaluate the tolerability and efficacy of dCD133KDEL in a systemic human breast carcinoma model. Time course viability studies showed that dCD133KDEL selectively inhibited MDA-MB-231 ductal breast carcinoma cells that contained a minority CD133(+) subpopulation, implicating CD133(+) cells as a source for self-renewal within this cell line. Furthermore, systemic administration of dCD133KDEL caused regression or inhibition of tumor growth in mice bearing an intrasplenic MDA-MB-231 tumor challenge as a model for metastatic disease. In the same model, combined therapy with dCD133KDEL and another immunotoxin designed to target the bulk tumor mass was the m...Continue Reading

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Citations

Nov 19, 2013·Applied Microbiology and Biotechnology·Ruosen YuanYongge Wu
Aug 1, 2013·Targeted Oncology·Nate N WaldronDaniel A Vallera
Apr 1, 2013·Drug Delivery and Translational Research·Suresh Kumar SwaminathanJayanth Panyam
Jul 23, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Suresh Kumar SwaminathanJayanth Panyam
Jun 1, 2013·Gynecologic Oncology·Amy P N SkubitzDaniel A Vallera
Feb 24, 2017·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Jörg U SchmohlDaniel A Vallera
Dec 7, 2019·Current Stem Cell Research & Therapy·Plabon K DasFarhadul Islam
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May 31, 2016·Toxins·Jörg U Schmohl, Daniel A Vallera
Oct 24, 2020·Drug Delivery and Translational Research·Jin CaoJayanth Panyam
Feb 16, 2021·Frontiers in Pharmacology·Qinghui ZhengXuli Meng
Mar 4, 2021·International Journal of Nanomedicine·Li LvGuocheng Li

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