title: Efficacy of host-dendritic cell vaccinations with or without minor histocompatibility antigen loading, combined with donor lymphocyte infusion in multiple myeloma patients.
abstract: Donor lymphocyte infusions (DLI) can induce durable remissions in multiple myeloma (MM) patients, but this occurs rather infrequently. As the graft-versus-tumor (GvT) effect of DLI depends on the presence of host-dendritic cells (DCs), we tested in a phase I/II trial whether the efficacy of DLI could be improved by simultaneous vaccination with host-DCs. We also analyzed the possibility of further improving the GvT effect by loading the DCs with peptides of mismatched hematopoietic cell-specific minor histocompatibility antigens (mHags). Fifteen MM patients not responding to a first DLI were included. Eleven patients could be treated with a second equivalent dose DLI combined with DC vaccinations, generated from host monocytes (moDC). For four patients, the DC products did not meet the quality criteria. In four of the treated patients the DCs were loaded with host mHag peptides. Toxicity was limited and no acute GvHD occurred. Most patients developed objective anti-host T-cell responses and in one patient a distinct mHag-specific T-cell response accompanied a temporary clinical response. These findings confirm that DLI combined with host-DC vaccination, either unloaded or loaded with mHag peptides, is feasible, safe and capable of inducing host-specific T-cell responses. The limited clinical effects may be improved by developing more immunogenic DC products or by combining this therapy with immune potentiating modalities like checkpoint inhibitors.
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Oostvogels
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Kneppers
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Minnema
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R C
authors.initials: RC
authors.lastname: Doorn
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: L E
authors.initials: LE
authors.lastname: Franssen
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Aarts
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Emmelot
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Spierings
authors.affiliation: Department of Clinical Pharmacy, Cell Therapy Facility, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Slaper-Cortenbach
authors.affiliation: Department of Clinical Pharmacy, Cell Therapy Facility, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Westinga
authors.affiliation: Department of Immunohematology and Blood bank, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Goulmy
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Lokhorst
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Mutis
mesh_terms: D000951:Antigens, Neoplasm; D003713:Dendritic Cells / Q000637:transplantation*; D005260:Female; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D015778:Minor Histocompatibility Antigens; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D015778:Minor Histocompatibility Antigens