Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP181) Radioprotective efficacy and cytokine profile induced by a novel radioprotectant, ON01210.

Singh, Vijay1, Shafran, Randi1, Hieber, Kevin1, Seed, Thomas1, Sree Kumar, K.1, 1 Radiation Casualty Management Team, Bethesda, MD

ABSTRACT- Onconova Therapeutics Inc. (Onconova) has introduced the Novonex/Ex-Rad family of drugs, a new class of chemically engineered pharmaceuticals. These agents specifically target and differentially protect proliferating normal cells. Within this family of drugs, ON01210, a non-toxic and efficacious radioprotectant has been identified. ON01210 has been evaluated for radioprotective efficacy in C3H/HeN mice. If administered intraperitoneally, at 200 mg/kg of body weight, ON01210 protects a significant number of mice against a lethal dose of whole-body gamma irradiation. We investigated the induction of cytokines/growth factors in mice treated with ON01210. C3H/HeN mice were treated with 200 mg/kg ON01210. Animals were bled 24 h post drug administration. Sera samples were separated and evaluated for various cytokines using a sandwich ELISA and cytokine array. Each group contained six mice. ELISA for serum cytokines was carried out for G-CSF, IL-6, IL-12, and IFN-gamma. We could not detect significant levels of any cytokine tested by the ELISA. We further evaluated sera samples for 62 cytokines/growth factors using cytokine arrays. The results of cytokine arrays suggest that induction of various cytokines and chemokines such as IL-4, L-selectin, MCP-1, MCP-5, M-CSF, MIG, MIP-1 gamma, MIP-2, PF-4 occurred with ON01210. Since chemokines act on very primitive progenitor cells, radioprotective efficacy of this drug may be enhanced by combining it with other drugs which induce cytokines effective on committed progenitor cells.

Key words: ON01210, Cytokines, Radioprotectant, Radiation

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2005 RRS