Abstract B46: VLA-4 targeted nanoparticles carrying a novel anti-Myc prodrug prolongs survival in a mouse model of multiple myeloma.

The MYC oncoprotein drives multiple myeloma (MM) pathogenesis, but the utility of small molecule inhibitors of MYC-MAX dimerization is limited by poor efficacy. We determined the efficacy of lipase labile MYC-MAX inhibitor prodrug (MI1-PD) loaded nanoparticles targeted via integrin {alpha 4 beta1 α4β1) or Very Late Antigen-1 (VLA-4)} in myeloma mice. We hypothesized that NPs containing specific targeting to myeloma cells, would enhance the therapeutic efficacy of MI1-PD containing NPs. The antiproliferative activity of intergin VLA-4-Targeted MI-1PD NPs (iTM-NPs) was determined in mouse cell line (5TGM1) in vitro and its effect on the survival in C57Bl/KaLwRij-5TGM1 murine model of myeloma in vivo. iTM-NPs (approximately 20 nm in diameter, 5% w/w MI1-PD loading) under in vitro conditions exhibited inhibition of cell growth compared to the controls. Also, C57Bl/KaLwRij-5TGM1 mice that received intravenous injection of iTM-NPs demonstrated greater survival rate over the controls. These results demonstrate the feasibility of using VLA-4 targeted nanotherapy approach to improve the availability of anti-Myc small molecule inhibitors for multiple myeloma and other cancers. Citation Format: Deepti Sood Gupta, Dipanjan Pan, Grace Hu, Anagana Senpan, Xiaoxiao Yang, Edward V. Prochownik, Gregory M. Lanza, Michael H. Tomasson. VLA-4 targeted nanoparticles carrying a novel anti-Myc prodrug prolongs survival in a mouse model of multiple myeloma. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B46.