The encouraging results presented in this report will support our consideration for further development of this novel therapeutic duplet in the treatment of patients with NMIBC. After 1 hour, the purse string suture was removed and rats were stimulated to expel bladder contents. The intravesical therapy was administered weekly for a total of six weeks to mimic intravesical BCG therapy in humans. Two weeks after completion of the intravesical therapy, animals were sacrificed and tissues were harvested and processed for subsequent analysis. Figure 1 illustrates the study treatment schema. As previously described, the IL-15N72D mutein was generated through site-directed mutagenesis of IL-15 wild type and found to exhibit super agonist activity through improved interactions with the human IL-15Rb chain. The IL-15N72D mutein displayed,4 fold lower effective concentration than wildtype IL-15 and the super agonist activity was enhanced further by pre-association with either mouse or human IL-15Ra-Fc molecules. Overall, the IL-15N72D/IL-15Ra-Fc complex exhibited a 25-fold lower EC50 than IL-15 alone for supporting IL-15-dependent cell growth, indicating the complex provides highly potent biological activity. The enhanced activity of the IL-15N72D/IL-15Ra-Fc complex is likely the result of a combination of the increased binding activity of the N72D mutein to the IL-2Rbc complex, optimized cytokine trans-presentation by the IL-15Ra chain, the dimeric nature of the cytokine domain and its increased in vivo half-life compared to native IL-15. Recently, Xu et al. reported on the therapeutic efficacy of intravenous ALT-803 in a myeloma xenograft model and alluded to the possible mechanism behind ALT-803 activity. Briefly, a single dose of ALT-803, but not IL-15 alone, eliminated wellestablished 5T33P and MOPC-315P myeloma cells from the bone marrow of tumor-bearing mice and prolonged survival in myeloma-bearing mice. ALT-803 treatment stimulated CD8 cells to secrete IFN-c and promoted rapid expansion of CD8CD44 memory T-cells. These memory CD8 T- cells also exhibited nonspecific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-c had no direct effect on myeloma cell growth in vitro. Though ALT-803 lost its antimyeloma activity in tumor-bearing IFN-c knockout mice, it was able to retain its ability to promote CD8CD44 memory T-cell proliferation, indicating that ALT-803-mediated stimulation of CD8CD44 memory T-cells is IFN-c-independent. ALT-803 stands out as a potent immunostimulant that is capable of simultaneously activating the innate and adaptive arms of the immune system to elicit both rapid and long-lasting protective responses against infectious or neoplastic challenges to the host. Thus, we hypothesize that intravesical administration of ALT-803 plus BCG will provide durable and potent cell-mediated immune responses. In the current study, we confirmed that ALT-803 reduction in angiogenesis.