Immunity to Trop-1, a newly identified breast cancer antigen, inhibits the growth of breast cancer in mice.
This study describes the immunotherapeutic properties of vaccines that encode tumor-associated calcium signal transducer-1 (Trop-1), a newly identified breast cancer antigen, in mice with breast cancer. Previously we found that Trop-1 was over-expressed in cellular breast cancer vaccines that were highly enriched for cells that induced therapeutic CTL-mediated immune responses in mice with breast cancer, as compared with non-enriched vaccines. In this study, to determine if the expression of Trop-1 by cells in the enriched vaccine was responsible for its therapeutic benefits, an expression plasmid that specified the Trop-1 gene was transfected into the LM fibroblast cells, which was then used as a vaccine. To augment their immunogenic properties, the fibroblasts were genetically modified before Trop-1 DNA-transfer to secrete IL-2 and to express allogeneic MHC class I H-2K(b)-determinants. Mice with established breast cancer treated solely by immunization with fibroblasts modified to express Trop-1 developed CD8(+) cell-mediated immunity to the breast cancer cells. The immunity was sufficient to prolong the survival of mice with established breast cancer. In some instances, the immunity was sufficient to result in rejection of the tumor; the mice remained tumor free more than 60 days.
Lee
Byeong C
BC
Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
Jung
Mi Y
MY
Cho
Daeho
D
O-Sullivan
InSug
I
Cohen
Edward P
EP
Kim
Tae Sung
TS
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006183:H-2 Antigens; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D010957:Plasmids; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006183:H-2 Antigens; D007376:Interleukin-2