title: Interleukin 15 augments antitumor activity of cytokine gene-modified melanoma cell vaccines in a murine model.
abstract: Many studies have demonstrated that interleukin 15 (IL-15) is a cytokine with strong antitumor properties and have suggested its potential use in tumor immunotherapy. IL-15 exerts its effect on innate and acquired immunity with the most prominent action in NK cells and CD8(+) memory T cells. Therefore, many authors have proposed that IL-15 could be a good candidate for augmenting the efficacy of vaccination strategies. In our experiments, in a model of B78-H1 murine transplantable melanoma, tumor-bearing mice were treated with different cytokine-gene modified tumor cell vaccines (producing TNF-alpha, GM-CSF, IL-12 or IL-6/sIL-6R) followed by a series of IL-15 injections. In order to investigate the infiltration of treated tumors by leukocytes, immunohistochemical staining was performed. In every case, the combined therapy was superior to the treatment with either a vaccine or IL-15 alone. Tumors treated with the combination of B78-H1 melanoma cells secreting IL-12 (B78/IL-12 vaccine) and IL-15 were heavily infiltrated by granulocytes. IL-15, either alone or in combination with the B78/IL-12 vaccine, influenced infiltration of tumors with CD3(+) lymphocytes, CD4(+)and CD8(+). To our knowledge, this is the first report that shows the universal genetically-modified tumor cell vaccine-augmenting properties of IL-15. The cytokine can be useful as an adjuvant in cancer gene therapy in humans.
authors.affiliation: Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, 02-097 Warsaw, Poland.
authors.forename: Grzegorz W
authors.initials: GW
authors.lastname: Basak
authors.forename: Lukasz
authors.initials: L
authors.lastname: Zapala
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Wysocki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
authors.forename: Marek
authors.initials: M
authors.lastname: Jakóbisiak
authors.forename: Witold
authors.initials: W
authors.lastname: Lasek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D019409:Interleukin-15 / Q000378:metabolism*; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D017252:CD3 Complex; D019496:Cancer Vaccines; D016207:Cytokines; D019409:Interleukin-15