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One approach is to modify a cytocidal protein toxin to direct its action to a specific population of cancer cells. We created a targeted toxin in which the receptor\u2010binding and pore\u2010forming moiety of anthrax toxin, termed Protective Antigen (PA), was modified to redirect its receptor specificity to HER2, a marker expressed at the surface of a significant fraction of breast and ovarian tumors. The resulting fusion protein (mPA\u2010ZHER2) delivered cytocidal effectors specifically into HER2\u2010positive tumor cells, including a trastuzumab\u2010resistant line, causing death of the cells. No off\u2010target killing of HER2\u2010negative cells was observed, either with homogeneous populations or with mixtures of HER2\u2010positive and HER2\u2010negative cells. A mixture of mPA variants targeting different receptors mediated killing of cells bearing either receptor, without affecting cells devoid of these receptors. Anthrax toxin may serve as an effective platform for developing therapeutics to ablate cells bearing HER2 or other tumor\u2010specific cell\u2010surface markers.<\/jats:p>","DOI":"10.1016\/j.molonc.2012.12.003","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T23:16:49Z","timestamp":1355872609000},"page":"440-451","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":65,"title":["Targeting HER2\u2010positive cancer cells with receptor\u2010redirected anthrax protective antigen"],"prefix":"10.1002","volume":"7","author":[{"given":"Andrew J.","family":"McCluskey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Olive","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Starnbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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