Researchers at Wake Forest School of Medicine have developed novel potent cytotoxins based on a platform of the tumor suppressor protein ephrinA1 as a targeting delivery protein. The cytotoxins have been tested in vivo against human Glioblastoma multiforme (GBM) cells and in vitro against GBM, breast and prostate cancer cells, all of which over-express the EphA2 receptors. The cytotoxic conjugates selectively kill these cancer cells while sparing normal cells, representing excellent candidates for developing targeted therapeutics for various solid tumor cancers, such as GBM, head, neck, pancreatic, ovarian and prostate cancers.
Benefits of these Novel Potent Cytotoxins that Selectively Kill Cancer Cells
- EphrinA1-derived cytotoxins result in 56 percent tumor reduction in mice harboring human GBM xenograft tumors with no observed toxicity
- Cytotoxins potently bind to, internalize and kill GBM, prostate and breast cancer cells in vitro with IC50 in the 10-11 M range
- Cytotoxins are specific for cancer cells over-expressing the EphA2 receptor and do not target normal cells
- The cytotoxins selectively target cells over-expressing EphA2 in solid tumors, resulting in highly targeted drug delivery for various cancers
- Both EphA2 and IL-13Ra2 targeted cytotoxins potently kill human GBM cells, and a combinatorial therapeutic scheme targeting the EphA2, IL-13Ra2 and Fra-1 proteins, which are over-expressed in at least 95 percent of GBM, may be effective in all GBM patients
- Waldemar Debinski, MD, PhD
- Jill Wykosky, PhD
- Denise Gibo, BS
- Wykosky et al. Mol Cancer Ther 2007; 6(12), 3208-3218
- Wykosky et al. Clin Cancer Res 2008; 14(1), 199-208
- US Patent application 12/201,662.
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