Onconase (ranpirnase)

In the present study, we compared a recombinant E. coli-derived ASNase marketed in Europe (Spectrila®) with an E. coli-derived ASNase preparation from India (Onconase) marketed in Eastern European countries. Our results reveal that Spectrila® met all of the testing parameters, stood out for its excellent quality and, thus, represents a safe treatment option in ALL. These findings are particularly important for low- and middle-income countries, where access to ASNase formulations is limited.

In cells infected by viruses, ONC hampers viral spread by digesting the primer tRNAs necessary for viral DNA replication. In this scenario, new therapeutic tools might be developed by exploiting the action of ONC-elicited RNA derivatives.

Data suggest that several known ONC anti-proliferative and anti-metastatic activities in A375 melanoma cells might depend on the upregulation of onco-suppressor miRNAs. Notably, miRNAs stability depends on the upstream regulation by long-non-coding-RNAs or circular-RNAs that can, in turn, be damaged by ONC ribonucleolytic activity.

This study expands the variety of RNase domain-swapped dimeric structures, underlining the unpredictability of the open interface arrangement upon domain swapping. Structural data also offer valuable insights to analyze the differences in the measured ONC or ONC-D biological activities.

The molecular dynamic simulations confirmed protein stability and the ability of scFv-ranpirnase (rantoxin) to bind to epidermal growth factor receptor protein...The immunotoxin function was assessed in A431 cancer cells and EGFR-negative HEK293 cells, and IC  values were estimated to be 22.4 ± 3 and >620.4 ± 5 nM, respectively. The results indicated that the immunotoxins produced in this study had the potential for use as anticancer drugs.

One of the most used by clinicians is olaparib, that, however, showed again cancer resistance in patients. Moreover, we underline that A375 cells treated for a prolonged time with AZD2461 were definitely more susceptible than parental A375 cells to the pro-apoptotic action of ONC. Considering also the different inhibitory effects of the two drugs on TNF-α gene expression and NF-kB DNA-binding, the tuning of their combined delivery to the A375 tumor cell line might open a promising scenario for future therapeutic applications devoted to defeat human melanoma.