title: Vaccination against prostate cancer using a live tissue factor deficient cell line in Lobund-Wistar rats.
abstract: Reducing expression of the tissue factor gene in prostate adenocarcinoma cells (PAIII) results in a cell line that, in vivo, mimics the growth of wildtype (wt) PAIII. However, instead of continuing to grow and metastasize as wt PAIII tumors do, tissue factor deficient PAIII (TFD PAIII) masses spontaneously regress after several weeks. Although whole cell vaccines are typically inactivated prior to administration to prevent proliferation within the host, numerous studies have suggested that exposure to live, attenuated, whole tumor cells, and the extracellular microenvironment they recruit, increases immunotherapeutic potential. Here, we provide support for this notion, and a strategy through which to implement it, by demonstrating that subcutaneous vaccinations with the TFD PAIII protect the Lobund-Wistar rat against subsequent wt PAIII cell challenge. TFD PAIII immunized rats suffered significantly less metastasis of wt PAIII challenge tumors compared to unvaccinated naïve controls rats. These results offer the intriguing possibility that the TFD PAIII vaccine is an effective system for the prevention and, possibly, the treatment of prostate cancer.
authors.affiliation: University of Notre Dame Biological Sciences, Notre Dame, IN, USA. jheinric@nd.edu
authors.forename: Julie E
authors.initials: JE
authors.lastname: Heinrich
authors.forename: Morris
authors.initials: M
authors.lastname: Pollard
authors.forename: William A
authors.initials: WA
authors.lastname: Wolter
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.forename: Elliot D
authors.initials: ED
authors.lastname: Rosen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Suckow
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control*; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003001:Cloning, Molecular; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000172:deficiency*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D013925:Thromboplastin