Antileukemic activity of Flt3 ligand in murine leukemia

Abing Wang, Stephen E. Braun, Guru Sonpavde, Kenneth Cornetta

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Flt3-ligand (Flt3-L) is an early acting costimulatory cytokine that has been shown to possess antitumor properties in murine solid tumor models. Flt3-L is a trans-membrane protein (tm) but can be proteolytically cleaved to a soluble form, which is also biologically active. In this study, the antitumor effect of both soluble and tmFlt3-L was evaluated in a mouse leukemia model. To mimic the multiorgan involvement characteristic of human leukemia, a factor-dependent cell line FDC.P1 was made leukemogenic by transfection with the human BCR/ABL gene. The resulting cell line, AW, expresses BCR/ABL RNA and protein. It maintains a similar in vitro growth rate as the parent cell line, but unlike the parent cell line, AW cells are factor independent and tumorigenic. Growth of FDC.P1 and AW cells are unaffected by the addition of soluble human Flt3-L to the culture medium. Also, AW growth is unaltered after transduction with a retroviral vector expressing the tm isoform of human Flt3-L (AW/tmFlt3-L). When 105 AW cells were i.v. injected into syngeneic DBA/2 mice, fatal leukemia developed in nine of nine (100%) mice within 4-6 weeks with involvement of the blood, bone marrow, spleen, and thymus. Systematic administration of soluble human Flt3-L (500 μg/kg/day) for 10 days protected mice from leukemia, with 11 of 17 mice tumor free at week 8 (64.7%). The tm isoform of Flt3-L also was protective. When 104 AW/tmFlt3-L cells were injected i.v. into mice, only 35.7% (5 of 14) developed leukemia versus 100% in control groups. Adoptive transfer of immunity was also demonstrated; T cells obtained from tumor-free animals conferred protection to 87% (seven of eight) naive mice challenged with AW cells. These results demonstrate that both soluble and membrane-bound human Flt3-L has antitumor activity in this leukemia model.

Original languageEnglish
Pages (from-to)1895-1900
Number of pages6
JournalCancer Research
Volume60
Issue number7
StatePublished - Apr 1 2000

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Leukemia
Cell Line
Membrane Proteins
Protein Isoforms
Growth
Neoplasms
Inbred DBA Mouse
Adoptive Transfer
Adaptive Immunity
Thymus Gland
Transfection
Culture Media
flt3 ligand protein
Spleen
Bone Marrow
RNA
Cytokines
T-Lymphocytes
Control Groups
Membranes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wang, A., Braun, S. E., Sonpavde, G., & Cornetta, K. (2000). Antileukemic activity of Flt3 ligand in murine leukemia. Cancer Research, 60(7), 1895-1900.

Antileukemic activity of Flt3 ligand in murine leukemia. / Wang, Abing; Braun, Stephen E.; Sonpavde, Guru; Cornetta, Kenneth.

In: Cancer Research, Vol. 60, No. 7, 01.04.2000, p. 1895-1900.

Research output: Contribution to journalArticle

Wang, A, Braun, SE, Sonpavde, G & Cornetta, K 2000, 'Antileukemic activity of Flt3 ligand in murine leukemia', Cancer Research, vol. 60, no. 7, pp. 1895-1900.
Wang A, Braun SE, Sonpavde G, Cornetta K. Antileukemic activity of Flt3 ligand in murine leukemia. Cancer Research. 2000 Apr 1;60(7):1895-1900.
Wang, Abing ; Braun, Stephen E. ; Sonpavde, Guru ; Cornetta, Kenneth. / Antileukemic activity of Flt3 ligand in murine leukemia. In: Cancer Research. 2000 ; Vol. 60, No. 7. pp. 1895-1900.
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