Dendritic cell-tumor cell fusion and staphylococcal enterotoxin B treatment in a pancreatic tumor model.
BACKGROUND
Surgical resection of pancreatic tumors removes gross disease but not metastases. Adjuvant therapy such as chemotherapy and radiation treatment is of little value in metastatic pancreatic cancer. The hypothesis of this investigation is that specific and effective immunotherapeutic vaccine (dendritic/tumor cell fusion) will activate cytotoxic T lymphocytes (CTLs), leading to the eradication of spontaneous pancreatic cancer.


METHODS
We have developed a double transgenic mouse model (MET) that forms spontaneous pancreatic tumors and expresses the human MUC1 antigen. Seven-week-old MET mice (n = 8) were treated every 3 weeks with the vaccine. In addition, these mice received 50 microg of superantigen staphylococcal enterotoxin B (SEB), a known T cell stimulant, prior to the first vaccination. A second treatment group received SEB alone (n = 8) and controls received no treatment (n = 9). MUC1-specific CTLs were measured by chromium release assay. At 10 weeks of age and at necropsy, MUC1 serum levels were measured using a MUC1-specific ELISA.


RESULTS
Mice were known to harbor microscopic foci of cancer at birth. Survival was enhanced in vaccine as well as SEB-treated mice (75% CI +/- 0.42) compared to controls (11% CI +/- 0.28) and both groups of treated mice exhibited mature CTLs without in vitro stimulation. MUC1 serum levels of the vaccine group were 50% less than that of control (P < 0.04) at 10 weeks. MUC1 serum levels directly correlated with tumor weight at necropsy (r = 0.86).


CONCLUSIONS
This is the first evidence that MUC1-specific CTLs can be stimulated to enhance survival in a spontaneous tumor model.
McConnell
Elizabeth J
EJ
Department of Surgery, Mayo Clinic Scottsdale, Arizona 85259, USA.
Pathangey
Latha B
LB
Madsen
Cathy S
CS
Gendler
Sandra J
SJ
Mukherjee
Pinku
P
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002459:Cell Fusion; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000494:pharmacology*; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000097:blood / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D004768:Enterotoxins; D018396:Mucin-1; C031818:enterotoxin B, staphylococcal