title: Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer.
abstract: A number of antitumor vaccines have recently shown promise in upregulating immune responses against tumor antigens and improving patient survival. In this study, we examine the effectiveness of vaccination using interleukin (IL)-15-expressing tumor cells and also examine their ability to upregulate immune responses to tumor antigens. We demonstrated that the coexpression of IL-15 with its receptor, IL-15Rα, increased the cell-surface expression and secretion of IL-15. We show that a gene transfer approach using recombinant adenovirus to express IL-15 and IL-15Rα in murine TRAMP-C2 prostate or TS/A breast tumors induced antitumor immune responses. From this, we developed a vaccine platform, consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells coexpressing IL-15 and IL-15Rα that inhibited tumor formation when mice were challenged with tumor. Inhibition of tumor growth led to improved survival when compared with animals receiving cells expressing IL-15 alone or unmodified tumor cells. Animals vaccinated with tumor cells coexpressing IL-15 and IL-15Rα showed greater tumor infiltration with CD8(+) T and natural killer (NK) cells, as well as increased antitumor CD8(+) T-cell responses. Vaccination with IL-15/IL-15Rα-modified TS/A breast cancer cells provided a survival advantage to mice challenged with unrelated murine TUBO breast cancer cells, indicating the potential for allogeneic IL-15/IL-15Rα-expressing vaccines.
authors.affiliation: 1] Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA [2] Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Ramlogan-Steel
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Black
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mannan
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Allison
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
authors.affiliation: 1] Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA [2] Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA [3] School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Steel
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor / Q000378:metabolism / Q000637:transplantation; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis*; D053720:Interleukin-15 Receptor alpha Subunit / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014611:Vaccination
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit