title: An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment.
abstract: Acute leukemias with adverse prognostic features carry a high relapse rate without allogeneic stem cell transplantation (allo-SCT). Allo-SCT has a high morbidity and is precluded for many patients because of advanced age or comorbidities. Postremission therapies with reduced toxicities are urgently needed. The murine acute leukemia model C1498 was used to study the efficacy of an intravenously administered vaccine consisting of irradiated leukemia cells loaded with the natural killer T (NKT)-cell agonist α-galactosylceramide (α-GalCer). Prophylactically, the vaccine was highly effective at preventing leukemia development through the downstream activities of activated NKT cells, which were dependent on splenic langerin(+)CD8α(+) dendritic cells and which led to stimulation of antileukemia CD4(+) and CD8(+) T cells. However, hosts with established leukemia received no protective benefit from the vaccine, despite inducing NKT-cell activation. Established leukemia was associated with increases in regulatory T cells and myeloid-derived suppressor cells, and the leukemic cells themselves were highly suppressive in vitro. Although this suppressive environment impaired both effector arms of the immune response, CD4(+) T-cell responses were more severely affected. When cytarabine chemotherapy was administered prior to vaccination, all animals in remission posttherapy were protected against rechallenge with viable leukemia cells.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand;
authors.forename: John D
authors.identifier: http://orcid.org/0000-0002-4772-7640
authors.initials: JD
authors.lastname: Gibbins
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand;
authors.forename: Lindsay R
authors.identifier: http://orcid.org/0000-0002-9572-8752
authors.initials: LR
authors.lastname: Ancelet
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; Capital and Coast District Health Board, Wellington Hospital, Wellington, New Zealand; Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand; and.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0003-3645-7988
authors.initials: R
authors.lastname: Weinkove
authors.affiliation: Ferrier Research Institute, Victoria University of Wellington, Petone, New Zealand.
authors.forename: Benjamin J
authors.identifier: http://orcid.org/0000-0002-5245-9767
authors.initials: BJ
authors.lastname: Compton
authors.affiliation: Ferrier Research Institute, Victoria University of Wellington, Petone, New Zealand.
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand;
authors.forename: Troels R
authors.initials: TR
authors.lastname: Petersen
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand; School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand;
authors.forename: Ian F
authors.identifier: http://orcid.org/0000-0002-7584-887X
authors.initials: IF
authors.lastname: Hermans
mesh_terms: D000208:Acute Disease; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007694:Killer Cells, Natural / Q000528:radiation effects / Q000637:transplantation*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011379:Prognosis; D055502:Secondary Prevention / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; C485184:enhanced green fluorescent protein; D003561:Cytarabine; D049452:Green Fluorescent Proteins