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October 2002, Volume 16, Number 10, Pages 1974-1983
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Review
Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods
R Stripecke1,2, A M Levine2, V Pullarkat2 and A A Cardoso3

1Institute for Genetic Medicine, University of Southern California, Los Angeles, CA, USA

2Division of Hematology, Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

3Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Correspondence to: R Stripecke, Institute for Genetic Medicine, 2250 Alcazar St. CSC-240, Los Angeles, CA 90033, USA; Fax: (323) 442-2764

Abstract

Adult patients with acute leukemia have, in general, a poor prognosis, with long-term, disease-free survival achieved in only approximately one-third of cases. One of the proposed mechanisms for this poor overall response is the inability of the immune system to detect and eliminate residual malignant leukemia cells, which subsequently serve as a source of leukemic relapse. This review discusses the rationale of immunotherapy for acute leukemia and presents in vitro and in vivo model systems that were devised for pre-B acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). New advances in the ex vivo manipulation of acute leukemia cells are presented, which attempt to modify these cells into functional antigen-presenting cells. These cells can then be used as autologous vaccines at the time of minimal residual disease after standard chemotherapy, to stimulate host immune responses against their own leukemia cells. The various approaches toward this aim include incubation of leukemia cells with cytokines or growth factors and gene manipulation of these cells. In particular, ex vivo culture of ALL cells with CD40 ligand, incubation of AML cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4) and lentiviral transduction of ALL and AML cells for expression of immunomodulators (CD80 and GM-CSF) are current approaches under investigation for the development of autologous acute leukemia cell vaccines.

Leukemia (2002) 16, 1974-1983. doi:10.1038/sj.leu.2402701

Keywords

AML; ALL; CD40L; GM-CSF; CD80; immunotherapy; gene therapy; lentivirus

Received 5 April 2002; accepted 27 May 2002
October 2002, Volume 16, Number 10, Pages 1974-1983
Table of contents    Previous  Abstract  Next   Full text  PDF
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