title: Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL).
abstract: Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8(+) T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71%) patients screened, CD8(+) T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8(+) T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8(+) T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8(+) T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology and Dendritic Cell Bank, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
authors.forename: Daphné
authors.initials: D
authors.lastname: Benteyn
authors.forename: An M T
authors.initials: AM
authors.lastname: Van Nuffel
authors.forename: Sofie
authors.initials: S
authors.lastname: Wilgenhof
authors.forename: Jurgen
authors.initials: J
authors.lastname: Corthals
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Aude
authors.initials: A
authors.lastname: Bonehill
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002465:Cell Movement; D003713:Dendritic Cells / Q000637:transplantation*; D018274:Electroporation; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000628:therapy*; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D012008:Recurrence; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes