Selective targeting of metastatic ovarian cancer using an engineered anthrax prodrug activated by membrane-anchored serine proteases

• DOI: 10.1073/pnas.2201423119
• Publication Date: 2022-07-08T18:40:47Z
• Authors: Nadire Duru; Nisha R. Pawar; Erik W. Martin; Marguerite S. Buzza; Gregory D. Conway; Rena G. Lapidus; Shihui Liu; Jocelyn Reader; Gautam G. Rao; Dana M. Roque; Stephen H. Leppla; Toni M. Antalis
• Keywords: Ovarian tumor; Anthrax toxin

Treatments for advanced and recurrent ovarian cancer remain a challenge due to lack of potent, selective, effective therapeutics. Here, we developed the basis transformative anticancer strategy based on anthrax toxin that has been engineered be selectively activated by catalytic power zymogen-activating proteases surface malignant tumor cells induce cell death. Exposure is cytotoxic lines spheroids derived from patient ascites. Preclinical studies demonstrate treatment induces regression in several vivo models, including patient-derived xenografts, without adverse side effects, supportive progression toward clinical evaluation. These data lay groundwork developing therapeutics treating women with late-stage cancers, utilizing mechanism distinct current therapies.