title: Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia.
abstract: 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.
authors.affiliation: Department of Pediatric Research, The National Hospital, Oslo, Norway. silvija.jankovic@klinmed.uio.no
authors.forename: Silvija
authors.initials: S
authors.lastname: Jarnjak-Jankovic
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Pettersen
authors.forename: Stein
authors.initials: S
authors.lastname: Saebøe-Larssen
authors.forename: Finn
authors.initials: F
authors.lastname: Wesenberg
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
mesh_terms: 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
chemical_list: D019496:Cancer Vaccines; D012333:RNA, Messenger
references.citation: J Exp Med. 1999 Dec 6;190(11):1669-78
references.pmid: 10587357
references.citation: J Exp Med. 2000 Dec 4;192(11):1535-44
references.pmid: 11104796
references.citation: J Exp Med. 2000 Mar 20;191(6):927-36
references.pmid: 10727455
references.citation: Leukemia. 2000 Dec;14(12):2193-4
references.pmid: 11187910
references.citation: Cancer Res. 2001 Mar 15;61(6):2386-9
references.pmid: 11289101
references.citation: Blood. 2001 Jun 1;97(11):3505-12
references.pmid: 11369644
references.citation: Int J Cancer. 2001 Aug 15;93(4):539-48
references.pmid: 11477558
references.citation: J Immunol. 2001 Nov 1;167(9):4844-52
references.pmid: 11673488
references.citation: Cancer Res. 2001 Dec 1;61(23):8513-9
references.pmid: 11731436
references.citation: J Immunol Methods. 2002 Jan 1;259(1-2):191-203
references.pmid: 11730854
references.citation: Lancet Oncol. 2001 Oct;2(10):597-607
references.pmid: 11902549
references.citation: Cancer Res. 2002 Apr 15;62(8):2347-52
references.pmid: 11956095
references.citation: Gene Ther. 2003 Mar;10(5):367-74
references.pmid: 12601391
references.citation: Hematology. 2003 Apr;8(2):97-104
references.pmid: 12745659
references.citation: J Immunol. 2003 Jun 15;170(12):5892-6
references.pmid: 12794115
references.citation: Immunology. 2003 Jul;109(3):374-83
references.pmid: 12807483
references.citation: Blood. 2004 Mar 1;103(5):1763-9
references.pmid: 14615377
references.citation: J Immunol Methods. 2004 Feb 15;285(2):171-80
references.pmid: 14980432
references.citation: Nat Rev Immunol. 2004 Apr;4(4):301-8
references.pmid: 15057788
references.citation: Nat Med. 2004 May;10(5):475-80
references.pmid: 15122249
references.citation: Immunity. 2004 May;20(5):539-50
references.pmid: 15142523
references.citation: Cancer Immunol Immunother. 2004 Oct;53(10):855-64
references.pmid: 15175905
references.citation: Nat Med. 1996 Jan;2(1):52-8
references.pmid: 8564842
references.citation: J Exp Med. 1996 Jan 1;183(1):87-97
references.pmid: 8551248
references.citation: J Exp Med. 1996 Jan 1;183(1):283-7
references.pmid: 8551233
references.citation: J Immunol. 1996 Apr 15;156(8):2918-26
references.pmid: 8609412
references.citation: J Immunol Methods. 1996 May 27;191(2):131-42
references.pmid: 8666832
references.citation: Br J Haematol. 1996 Jul;94(1):82-8
references.pmid: 8757513
references.citation: Prostate. 1996 Dec;29(6):371-80
references.pmid: 8977634
references.citation: Curr Opin Immunol. 1997 Feb;9(1):10-6
references.pmid: 9039784
references.citation: J Exp Med. 1997 Oct 6;186(7):1177-82
references.pmid: 9314567
references.citation: Blood. 1997 Nov 1;90(9):3245-87
references.pmid: 9345009
references.citation: Nat Med. 1998 Mar;4(3):328-32
references.pmid: 9500607
references.citation: Nature. 1998 Mar 5;392(6671):86-9
references.pmid: 9510252
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9482-7
references.pmid: 9689106
references.citation: J Exp Med. 2000 Feb 7;191(3):423-34
references.pmid: 10662788
references.citation: Cancer Res. 2000 Jul 1;60(13):3542-9
references.pmid: 10910067
references.citation: Cancer Res. 2000 Nov 15;60(22):6441-7
references.pmid: 11103811
references.citation: Acta Paediatr. 1998 Nov;87(11):1151-61
references.pmid: 9846917