Abstract 1249: Potent immunomodulatory effects of lenalidomide enhance the effect of a therapeutic vaccine against established lymphoma in mice .

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Lenalidomide is an effective therapeutic agent with direct inhibitory effects on malignant B- and plasma cells and immunomodulatory effects on the T cell activation. The dual function of lenalidomide makes it an appealing candidate for combination with other novel cancer agents. We investigated the immune stimulatory effects of lenalidomide, administrated to mice in doses which provided comparable pharmacokinetics to human patients, on the potency of a novel fusion DNA lymphoma vaccine. The combination protected mice from lethal challenge with syngeneic A20 murine lymphoma, resulting in significantly improved survival compared with vaccine or lenalidomide alone and induced immune memory. In vivo depletion experiments demonstrated a requirement for effector CD8+ and CD4+ T cells. Surprisingly, lenalidomide alone was associated with reduced numbers of systemic immune suppressive cells (MDSC/Treg) in tumor-bearing, but not naive mice, an effect that was independent of simple tumor burden reduction. Finally, the combination of lenalidomide and vaccine produced significantly improved survival in mice with 7 day established tumors. These results demonstrated the dual effect of lenalidomide on enhancing antigen-specific T-cell immunity and a novel mechanism of action reversing tumor-induced immune suppression, which makes it ideal for combination with vaccines as an immune adjuvant. Citation Format: Ippei Sakamaki, Larry W. Kwak, Soung-chul Cha, Qing Yi, Beatrisa Lerman, Jian Chen, Sekhar Surapaneni, Scott Bateman, Hong Qin. Potent immunomodulatory effects of lenalidomide enhance the effect of a therapeutic vaccine against established lymphoma in mice . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1249. doi:10.1158/1538-7445.AM2013-1249