Flt3 ligand delivered in a pluronic formulation prolongs the survival of mice with orthotopic pancreatic adenocarcinoma

Abdelkader E. Ashour, Heth R. Turnquist, Nicole Burns, Xiaojian Wang, Xuede Lin, Jarrod Tremayne, Michael A Hollingsworth, Joan M. Blonder, Gary J. Rosenthal, James E Talmadge, Joyce C Solheim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Pancreatic adenocarcinoma is a devastating disease, characterized by asymptomatic development and extremely poor prognosis. Given the resistance of pancreatic cancer to standard chemo- and radiotherapy, we have focused on the development of immunotherapies for this disease. The number of dendritic cells (DCs), natural killer (NK) cells, and T-cells in the blood and secondary lymphoid organs is regulated by a group of hematopoietic growth factors, which includes fins-like tyrosine kinase-3 ligand (Flt3L). We have demonstrated previously that the bioavailability and in vivo half-life of Flt3L are increased by Flt3L formulation in the pluronic ProGelz®. In this study, we first examined the effectiveness of Flt3L delivered in ProGelz against subcutaneous (s.c.) pancreatic adenocarcinomas in mice. We found that an intramuscular (i.m.) injection of Flt3L in ProGelz significantly increased the survival of mice bearing s.c. pancreatic tumors, compared to the administration of phosphate-buffered saline (PBS) in ProGelz. We then tested Flt3L in ProGelz in an orthotopic pancreatic tumor model, and demonstrated that it significantly enhanced the survival of tumor-bearing mice, compared to PBS in ProGelz. Overall, these observations suggest that Flt3L formulated in ProGelz may have potential clinical utility as a treatment for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)235-238
Number of pages4
JournalCancer Biotherapy and Radiopharmaceuticals
Volume22
Issue number2
DOIs
StatePublished - Apr 1 2007

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Poloxamer
Protein-Tyrosine Kinases
Adenocarcinoma
Ligands
Pancreatic Neoplasms
Phosphates
Asymptomatic Diseases
Neoplasms
Intramuscular Injections
flt3 ligand protein
Natural Killer Cells
Immunotherapy
Dendritic Cells
Biological Availability
Half-Life
Intercellular Signaling Peptides and Proteins
Radiotherapy
T-Lymphocytes
Drug Therapy

Keywords

  • Cytokine
  • Dendritic cell
  • Flt3L
  • Immunotherapy
  • Mice
  • Orthotopic
  • Pancreatic cancer
  • ProGelz
  • Tumor immunology

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Flt3 ligand delivered in a pluronic formulation prolongs the survival of mice with orthotopic pancreatic adenocarcinoma. / Ashour, Abdelkader E.; Turnquist, Heth R.; Burns, Nicole; Wang, Xiaojian; Lin, Xuede; Tremayne, Jarrod; Hollingsworth, Michael A; Blonder, Joan M.; Rosenthal, Gary J.; Talmadge, James E; Solheim, Joyce C.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 22, No. 2, 01.04.2007, p. 235-238.

Research output: Contribution to journalArticle

Ashour, Abdelkader E. ; Turnquist, Heth R. ; Burns, Nicole ; Wang, Xiaojian ; Lin, Xuede ; Tremayne, Jarrod ; Hollingsworth, Michael A ; Blonder, Joan M. ; Rosenthal, Gary J. ; Talmadge, James E ; Solheim, Joyce C. / Flt3 ligand delivered in a pluronic formulation prolongs the survival of mice with orthotopic pancreatic adenocarcinoma. In: Cancer Biotherapy and Radiopharmaceuticals. 2007 ; Vol. 22, No. 2. pp. 235-238.
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