Journal of Vaccines & Vaccination

Abstract

Bicelin (B-Cell Lymphoma 2 Inhibitor) a Highly Safe DNA-based Anti-Cancer Drug Showed no in vivo Cytopenia, Nephrotoxicity and Hepatotoxicity

Reza Sheikhnejad*, Farzaneh Ashrafi, Ardeshir Talebi, Bahar Mazaheri, Fatemeh Moslemi and Mehdi Nematbakhsh

Background: Non-Hodgkin's lymphoma is the seventh most common cancer in clinic. Lymphoma could be treated with newly developed anti-apoptotic small molecule inhibitors of bcl-2 such as ABT-199 or venetoclax. However most small molecules present numerous side effects and cancer becomes resistance to them rapidly. PNT100 is a DNA- based bcl-2 inhibitor that has shown great efficacy and safety in treating non-Hodgkin's lymphoma tumors. However, liposomal carrier (smarticles) that was used to deliver PNT100 eventually failed to produce robust efficacy in the latest clinical trial conducted by ProNai Therapeutics (now called Sierra Technology). The high cost of liposomal carriers, makes this targeted drug less affordable. In addition, the liposomal components may also present some minor side effects as reported in pilot phase II trial. In this study, we eliminated liposome and used a specific Epigenic modification to deliver this 24 bp oligonucleotides (PNT100) without using additional chemicals and named it Bicelin.

Methods: In this study, the safety of Bicelin was determined by evaluating the cytopenia, nephrotoxicity and hepatotoxicity effects of this drug in healthy animal model (Rats). The rats in experimental group were received Bicelin (20 mg/kg/day) for 5 days a week. The treatment was continued for 3 consecutive weeks. The blood and urine samples were collected for evaluation and the rats were then sacrificed. The kidneys and liver tissues were fixed in formalin 10% to perform histological investigation using H&E staining.

Results: The in vitro and in vivo results clearly demonstrate that Bicelin is target specific and highly safe. We observed no cytopenia when blood tests were performed after 15 consecutive injection of Bicelin; Urine analysis revealed no significant differences between experimental and control group and there was no nephrotoxicity or hepatotoxicity when kidney and liver tissues were examined.

Conclusion: Based on our in vitro and in vivo safety studies, our bcl2 inhibitor, Bicelin is much safer and about 10- fold more effective than its liposomal form (PNT2258). Considering preclinical, phase I and II studies of PNT2258, Bicelin is expected to be very safe and effective in clinic.

Published Date: 2021-06-29; Received Date: 2021-04-07