Pre-Clinical Data Show Intracellular Pathways Affected by ONCONASE®
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Alfacell Corporation has announced that in vitro and in vivo data presented at the 5th Cancer Drug Research & Development conference show the genes affected and biological pathways impacted by ONCONASE stimulated intracellular events as revealed by expression profiling of human malignant mesothelioma cell lines. Data presented also show that ONCONASE conjugates effectively kill human cancer cells in cell culture and murine models of cancer.
Susanna Rybak, Ph.D., a member of Alfacell's scientific advisory board, presented a poster entitled "ONCONASE (ranpirnase): Intracellular Activity and Extracellular Selectivity." The data demonstrated that 181 genes were consistently up- and down-regulated by ONCONASE and that the genes involved in triggering apoptosis (programmed cell death) and the intracellular MAPK signaling pathway were impacted by ONCONASE in vitro.
Additionally, pre-clinical data in mice demonstrated the relative potency of chemical conjugates of ONCONASE. These findings further support the research of next generation targeted ONCONASE fusion proteins in an effort to develop compounds with improved tumor penetrating abilities. The research was conducted in collaboration with Alfacell at Fox Chase Cancer Center and the University of Duisburg-Essen.
"This work may explain the intrinsic anti-tumor activity seen after ONCONASE treatment through the identification of the specific genes affected and the biological pathways impacted," said Dr. Rybak. "Additionally, this data is helping us to better understand the optimal intracellular pathways for developing antibody targeted ONCONASE compounds."
"The data presented further illuminates the potential for ONCONASE to simultaneously switch on and off numerous genes controlling major regulatory processes in the cell life cycle, and underscores that ONCONASE works selectively and does not appear to kill cells indiscriminately," added Kuslima Shogen, Alfacell's chief executive officer. "This research represents an important step forward in our continuing efforts to create targeted ONCONASE fusion proteins and to bring them forward into the clinic."
