Relationship of QBI-139, a human ribonuclease variant, and RNA in cancer cells.

Abstract

e13650 Background: RNA has been recognized as a drug target for cancer therapy, as evidenced by the ongoing clinical trials of RNAi and antisense therapies. An alternative approach that circumvents the delivery and stability issues of RNAi and antisense is to harness the activity of naturally occurring enzymes that degrade RNA. The EVade Ribonucleases (RNases) are variants of the native RNases that have been modified to diminish their binding to their natural inhibitor, allowing the EVade RNases to kill cancer cells. The efficacy of one of the EVade RNases, called QBI-139, in in vivo models of human cancer has been examined relative to FDA approved cancer therapies. Methods: QBI-139 has been tested in nude mouse xenograft models using a variety of tumor types and multiple cell lines within the different tumor types. Each model compared the efficacy of QBI- 139 with control groups which included: vehicle and an effective commercial drug specific for each tumor type (e.g. 5-fluorouracil or cisplatin). The human cancer cells were grown in culture and then implanted subcutaneously into the flanks of nu/nu mice. The tumors were allowed to grow to a measureable size and then drugs were administered once weekly. Tumor volumes and animal body weights were recorded twice weekly. The percent tumor growth inhibition (TGI) was used as a measure of efficacy was determined by comparing final and starting tumor volumes of groups treated with drug relative to the vehicle. Results: QBI-139 demonstrated a efficacy in prostate cancer that was similar to docetaxel with both agents causing >80% TGI. In addition, the safety profile of QBI-139 was better than docetaxel, which led to the death of two animals in that arm of the study. Additional results will be presented in colorectal and non-small cell lung cancer models. Conclusions: QBI-139 is a broadly efficacious agent that provides a new way to attack cancer and may provide an innovative new tool for oncologists. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Quintessence Biosciences, Inc. Quintessence Biosciences, Inc.