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Immunology

Lenalidomide enhances the protective effect of a therapeutic vaccine and reverses immune suppression in mice bearing established lymphomas

Leukemia volume 28, pages 329–337 (2014)Cite this article

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Abstract

Immunomodulatory drugs (IMiDs) are effective therapeutic agents with direct inhibitory effects on malignant B- and plasma-cells and immunomodulatory effects on the T-cell activation. This dual function of IMiDs makes them appealing candidates for combination with a cancer vaccine. 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 was curative in the majority of mice with 8d pre-established syngeneic A20 lymphomas compared with vaccine or lenalidomide alone and induced immune memory. In vivo depletion experiments established the requirement for effector CD8+ and CD4+ T cells in protective immunity. Unexpectedly, lenalidomide alone was also associated with reduced numbers of systemic myeloid-derived suppressor cell (MDSC) and regulatory T cell (Treg) in tumor-bearing but not naïve mice, an effect that was independent of simple tumor burden reduction. These results confirm and extend results from other models describing the effect of lenalidomide on enhancing T-cell immunity, highlight the potency of this effect, and provide a rationale for clinical application. Independently, a novel mechanism of action reversing tumor-induced immune suppression by MDSC is suggested.

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Acknowledgements

This work was supported by a contract from Celgene Corporation and by grants from the Leukemia and Lymphoma Society (TRP 6003-07 and SCOR 7262-08), Cancer Prevention and Research Institute of Texas (RP 100457) and Department of Defense (W81XWH-07) to LWK.

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Authors and Affiliations

  1. Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    I Sakamaki, L W Kwak, S-c Cha, Q Yi, B Lerman & H Qin

  2. Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    I Sakamaki, L W Kwak, S-c Cha, Q Yi, B Lerman & H Qin

  3. Celgene Corporation, Summit, NJ, USA

    J Chen, S Surapaneni & S Bateman

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  1. I Sakamaki
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Correspondence to L W Kwak.

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Competing interests

Larry W Kwak has been funded by Celgene. Jian Chen, Sekhar Surapaneni, Scott Bateman are employed by Celgene. The remaining authors declare no conflict of interest.

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Sakamaki, I., Kwak, L., Cha, Sc. et al. Lenalidomide enhances the protective effect of a therapeutic vaccine and reverses immune suppression in mice bearing established lymphomas. Leukemia 28, 329–337 (2014). https://doi.org/10.1038/leu.2013.177

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