title: Peptide vaccination induces profound changes in the immune system in patients with B-cell chronic lymphocytic leukemia.
abstract: Although the immune status of chronic lymphocytic leukemia (CLL) patients is mostly characterized by immunosuppression, there is an accumulation of in vivo (graft-versus-leukemia effect) and in vitro (spontaneous remissions after infections) data that indicates that CLL might be effectively targeted by T-cell based immunotherapy. Recently, we characterized receptor for hyaluronic acid mediated motility (RHAMM) as a preferential target for immunotherapy of CLL. We also completed a RHAMM-derived peptide vaccination phase I/II clinical trial in CLL. Here, we present a detailed immunological analysis of six CLL patients vaccinated with HLA-A2 restricted RHAMM-derived epitope R3 (ILSLELMKL). Beside effective induction of R3-specific cytotoxic T-cells, peptide vaccination caused profound changes in different T-cell subsets as well as cytokines. We present longitudinal analyses of Th17, CD8(+)CD103(+), CD8(+)CD137(+) and IL-17 producing CD8(+) T cells (CD8(+)IL- -17(+)) as well as important cytokines involved in regulation of immune response such as TGF-β, IL-10, IL-2 and TNF throughout the peptide vaccination period.
authors.affiliation: Department of Experimental Hematooncology, Medical University of Lublin, Poland. giannop@tlen.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
authors.forename: Paulina
authors.initials: P
authors.lastname: Własiuk
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszyńska
authors.forename: Jacek
authors.initials: J
authors.lastname: Roliński
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D010446:Peptide Fragments