*3.3. Therapeutic Implications*

Enhancement of ricin-induced cell death by TNF family cytokines presents new potential therapeutic targets against ricin toxicity. Targeting these cell death ligands directly with neutralizing antibodies represents a viable therapeutic option as does targeting ricin with neutralizing antibodies. We explored this previously at the cellular level [20]. Our identification of activated cell death pathways in response to ricin combined with TNF family cytokines reveals further potential therapeutic targets (i.e., specific components of each cell death pathway). However, the finding that di fferent cytokines induce distinct cell death pathways in combination with ricin suggests that a combinatorial approach may be best in the context of ricin toxicity. Rather than targeting apoptosis, which would limit ricin/TRAIL-induced cell death only, both caspase-dependent apoptosis and cathepsin-dependent cell death should be targeted. In addition, we cannot rule out contributions from other cytokines and cell death pathways to ricin-induced cell death in the in vivo setting. This could result in the targeting of multiple cell death pathways at various steps to limit ricin-induced toxicity. Another potential therapeutic implication of this work may extend to the targeting of tumors, as we have utilized cell lines derived from cancerous tissue throughout this research. Recent research on cancer therapeutics has partly focused on transfection of cytotoxic genes into tumor cells [67]. Ricin may serve as a good candidate for such targeted cancer therapy, particularly if combined with administration of TNF family cytokines.
