Flt3 ligand delivered in a pluronic formulation prolongs the survival of mice with orthotopic pancreatic adenocarcinoma.
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 fms-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 ProGelzx. 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.
Ashour
Abdelkader E
AE
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Turnquist
Hēth R
HR
Burns
Nicole
N
Wang
Xiaojian
X
Lin
Xuede
X
Tremayne
Jarrod
J
Hollingsworth
Michael A
MA
Blonder
Joan M
JM
Rosenthal
Gary J
GJ
Talmadge
James E
JE
Solheim
Joyce C
JC
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D005260:Female; D007273:Injections, Intramuscular; D008565:Membrane Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D020442:Poloxamer; D015996:Survival Rate
D008565:Membrane Proteins; C084881:flt3 ligand protein; D020442:Poloxamer