title: The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells.
abstract: We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM.
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Willemen
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Johan M J
authors.initials: JM
authors.lastname: Van den Bergh
authors.affiliation: Department of Hematology and Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Bonte
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Anguille
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Barbara M H
authors.initials: BM
authors.lastname: Stein
authors.affiliation: Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Department of Hematology and Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Tessa
authors.initials: T
authors.lastname: Kerre
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.affiliation: Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Viggo F I
authors.initials: VF
authors.lastname: Van Tendeloo
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.|Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Evelien L J
authors.initials: EL
authors.lastname: Smits
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D018274:Electroporation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016326:Extracellular Matrix Proteins; D015234:HLA-A Antigens; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; C098946:hyaluronan-mediated motility receptor
keywords: electroporation; hyaluronan-mediated motility receptor; immunotherapy; messenger RNA; vaccination