title: In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice.
abstract: Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, IL7 or IL15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL7/IL15 fusion protein in which IL7 and IL15 are linked by a flexible linker. We then compared the antitumor effect of rIL7/IL15 with the individual factors rIL7 and/or rIL15. We show here that rIL7/IL15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs, and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL7/IL15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL7/IL15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL7/IL15 may offer a new tool to enhance antitumor immunity and treat cancer. Mol Cancer Ther; 15(10); 2413-21. ©2016 AACR.
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut. Medical College, Three Gorges University, Yichang, China.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut.
authors.forename: Debra
authors.initials: D
authors.lastname: Rood
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut. University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, Connecticut. laijun.lai@uconn.edu.
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000494:pharmacology; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019409:Interleukin-15; D015851:Interleukin-7; D011993:Recombinant Fusion Proteins