Format

Send to

Choose Destination
Blood. 2014 Nov 6;124(19):2953-63. doi: 10.1182/blood-2014-04-568956. Epub 2014 Sep 18.

An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment.

Author information

1
Malaghan Institute of Medical Research, Wellington, New Zealand; School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand;
2
Malaghan Institute of Medical Research, Wellington, New Zealand;
3
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.
4
Ferrier Research Institute, Victoria University of Wellington, Petone, New Zealand.

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.

PMID:
25237205
DOI:
10.1182/blood-2014-04-568956
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center