title: IL-15 receptor alpha as the magic wand to boost the success of IL-15 antitumor therapies: The upswing of IL-15 transpresentation.
abstract: Interleukin (IL)-15 as a stand-alone therapy can activate the antitumor functions of immune effector cells resulting in significant tumor regression. Interestingly, combining IL-15 with the α-moiety of its receptor (IL-15Rα), also called IL-15 transpresentation, increases the in vivo half-life of IL-15 and enhances binding of IL-15 with cells expressing the IL-15Rβγ, such as NK cells and CD8+T cells. These features enlarge the signal transmission of IL-15, resulting in improved proliferation and antitumor activities of both NK cells and CD8+T cells, eventually leading to enhanced killing of tumor cells. In this review, we discuss the antitumor strategies in which this IL-15 transpresentation mechanism is implemented, that are currently under preclinical investigation. Furthermore, we give an overview of the studies in which the IL-15/IL-15Rα complexes are combined with other antitumor therapies. The promising results in these preclinical studies have incited several clinical trials to test the safety and efficacy of IL-15 transpresentation strategies to treat both hematological and advanced solid tumors.
authors: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium. Electronic address: johan.vandenbergh@uantwerpen.be.
authors: Johan Mj
authors: JM
authors: Van den Bergh
authors: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium.
authors: Eva
authors: E
authors: Lion
authors: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium.
authors: Viggo Fi
authors: VF
authors: Van Tendeloo
authors: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium; Center for Oncological Research Antwerp, Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium.
authors: Evelien Ljm
authors: EL
authors: Smits
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000276:immunology; D053720:Interleukin-15 Receptor alpha Subunit / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit
keywords: Antitumor immunotherapies; Combination therapies; IL-15 receptor alpha; IL-15 transpresentation; Interleukin-15