Background: Prostate cancer is both the most common cancer diagnosis and the second most common cause of cancer-related death for men in the United States. An ideal new therapy would selectively deliver the drug to the tumor while also preventing toxicity in normal tissue.

Methods and Results: Recent exciting clinical advances with antibody drug conjugates have resulted in FDA approval of such tumor-targeting therapies. However, antibodies are difficult to chemically modify, require humanization, and their large size hinders tumor penetration. Aptamers - small nucleic acid ligands - have many advantages over traditional antibody targeting agents, including ease of synthesis, amenability to chemical modification, and reversibility. Moreover, they exhibit antibody-like target affinities and specificities at a fraction of the size, allowing more efficient tumor penetration.

We have identified an aptamer, termed E3, which selectively internalizes into prostate cancer cells, but does not target normal cells. Additionally, E3 targets and internalizes into a variety of other cancer types, including breast, ovarian, lung, colon, melanoma, glioblastoma, liver, and leukemia cancers. Linking the E3 aptamer to a deimmunized version of the Pseudomonas exotoxin (PE38) kills prostate cancer cells in vitro with an IC50 of 0.4-1.1 nM while displaying no measured toxicity towards normal cells, and linking E3 to the highly toxic auristatin drugs, MMAE or MMAF, kills prostate cancer cells in vitro with an IC50 of 5-12 nM. Significantly, E3 maintains its tumor-targeting abilities in vivo, targeting both prostate tumors and patient-derived colon cancer tumors in mice as evidenced by near-infrared in vivo imaging.

Conclusions: Together, these studies show the potential therapeutic benefit of E3 drug targeting for the treatment of prostate cancer.

Citation Format: Bethany Powell Gray, Linsley Kelly, Matthew Levy, Bruce A. Sullenger. A novel aptamer targeting agent for prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5523. doi:10.1158/1538-7445.AM2015-5523