title: Lenalidomide enhances the protective effect of a therapeutic vaccine and reverses immune suppression in mice bearing established lymphomas.
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.
authors.affiliation: 1] Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: I
authors.initials: I
authors.lastname: Sakamaki
authors.affiliation: 1] Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Kwak
authors.affiliation: 1] Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S-c
authors.initials: SC
authors.lastname: Cha
authors.affiliation: 1] Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Yi
authors.affiliation: 1] Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lerman
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Surapaneni
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bateman
authors.affiliation: 1] Department of Lymphoma and Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Qin
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007156:Immunologic Memory; D000077269:Lenalidomide; D008223:Lymphoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide