title: Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.
abstract: Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.
authors.affiliation: 1 Department of Obstetrics & Gynecology, University of Southern California , Los Angeles, California.|2 Norris Comprehensive Cancer Center, University of Southern California , Los Angeles, California.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Da Silva
authors.affiliation: 3 Department of Molecular Microbiology & Immunology, University of Southern California , Los Angeles, California.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Woodham
authors.affiliation: 4 Department of Internal Medicine, Wayne State University School of Medicine , Detroit, Michigan.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Naylor
authors.affiliation: 5 IRX Therapeutics, Inc. , New York, New York.
authors.forename: James E
authors.initials: JE
authors.lastname: Egan
authors.affiliation: 5 IRX Therapeutics, Inc. , New York, New York.
authors.forename: Neil L
authors.initials: NL
authors.lastname: Berinstein
authors.affiliation: 1 Department of Obstetrics & Gynecology, University of Southern California , Los Angeles, California.|2 Norris Comprehensive Cancer Center, University of Southern California , Los Angeles, California.|3 Department of Molecular Microbiology & Immunology, University of Southern California , Los Angeles, California.
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
mesh_terms: D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000821:virology; D027383:Papillomaviridae / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D016207:Cytokines; C114857:IRX 2