Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia.
BACKGROUND
Leukemia is a clonal disorder characterized by uncontrolled proliferation of haematopoietic cells, and represents the most common form of cancer in children. Advances in therapy for childhood leukemia have relied increasingly on the use of high-dose chemotherapy often combined with stem-cell transplantation. Despite a high success rate and intensification of therapy, children still suffer from relapse and progressive disease resistant to further therapy. Thus, novel forms of therapy are required.


METHODS
This study focuses on dendritic cell (DC) vaccination of childhood leukemia and evaluates the in vitro efficacy of different strategies for antigen loading of professional antigen-presenting cells. We have compared DCs either loaded with apoptotic leukemia cells or transfected with mRNA from the same leukemia cell line, Jurkat E6, for their capacity to induce specific CD4+ and CD8+ T-cell responses. Monocyte-derived DCs from healthy donors were loaded with tumor antigen, matured and co-cultured with autologous T cells. After one week, T-cell responses against antigen-loaded DCs were measured by enzyme-linked immunosorbent spot (ELISPOT) assay.


RESULTS
DCs loaded with apoptotic Jurkat E6 cells or transfected with Jurkat E6-cell mRNA were both able to elicit specific T-cell responses in vitro. IFNgamma-secreting T cells were observed in both the CD4+ and CD8+ subsets.


CONCLUSIONS
The results indicate that loading of DCs with apoptotic leukemia cells or transfection with tumour mRNA represent promising strategies for development of cancer vaccines for treatment of childhood leukemia.
Jarnjak-Jankovic
Silvija
S
Department of Pediatric Research, The National Hospital, Oslo, Norway. silvija.jankovic@klinmed.uio.no
Pettersen
Rolf D
RD
Saebøe-Larssen
Stein
S
Wesenberg
Finn
F
Gaudernack
Gustav
G
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000276:immunology / Q000517:prevention & control*; D010587:Phagocytosis; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D012333:RNA, Messenger
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