Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells.
Genetically modified mice with spontaneous development of mammary carcinoma provide a powerful tool to study the efficacy of tumor vaccines, since they mimic breast cancer development in humans. We used a transgenic murine model expressing polyomavirus middle T oncogene and mucin 1 tumor-associated Ag to determine the preventive effect of a dendritic/tumor fusion cell vaccine. The MMT (a transgenic murine model) mice developed mammary carcinoma between the ages of 65-108 days with 100% penetrance. No spontaneous CTL were detected. However, prophylactic vaccination of MMT mice with dendritic/tumor fusion cells induced polyclonal CTL activity against spontaneous mammary carcinoma cells and rendered 57-61% of the mice free of the disease at the end of experiment (180 days). Furthermore, the level of CTL activity was maintained with multiple vaccinations. The antitumor immunity induced by vaccination with dendritic/tumor fusion cells reacted differently to injected tumor cells and autochthonous tumor. Whereas the injected tumor cells were rejected, the autochthonous tumor evaded the attack and was allowed to grow. Collectively these results indicate that prophylactic vaccination with dendritic/tumor fusion cells confers sufficient antitumor immunity to counter the tumorigenesis of potent oncogenic products. The findings in the present study are highly relevant to cancers in humans.
Xia
Jianchuan
J
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Tanaka
Yasuhiro
Y
Koido
Shigeo
S
Liu
Chunlei
C
Mukherjee
Pinku
P
Gendler
Sandra J
SJ
Gong
Jianlin
J
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D002459:Cell Fusion / Q000379:methods; D002478:Cells, Cultured; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology; D009368:Neoplasm Transplantation / Q000379:methods / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000952:Antigens, Polyomavirus Transforming; D019496:Cancer Vaccines; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments