Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

Targeted expression of DT-A in ovarian cancer cells in vitro and in tumor cells in mouse models was performed by Huang et al [343] using poly(h-amino ester) polymers as a vector for nanoparticulate delivery of DNA. In these ovarian-specific antitumor constructs, the promoters of two genes, HE4 (WFDC2) and MSLN (which transcriptional activity is significantly enhanced in ovarian cancer cells relative to normal ovarian cells and cells in other tissues [383] [384] [385] [386] [387] [388] [389] ) were chosen to target the expression of DT-A gene to ovarian tumor cells. Significant reduction in tumor mass and a prolonged life span of xenografts bearing mice were observed as a result of DT-A nanoparticles administration directly to subcutaneous xenograft tumors and to the peritoneal cavity. Moreover, treatment with DT-A nanoparticles resulted in more efficient suppression of tumor growth compared to clinically relevant doses of the standard chemotherapeutics cisplatin and paclitaxel, with minimal nonspecific tissue and blood chemistry toxicity [343] .