Abstract
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-2Kb-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.
Original language | English |
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Pages (from-to) | 7757-7763 |
Number of pages | 7 |
Journal | Vaccine |
Volume | 28 |
Issue number | 49 |
DOIs | |
Publication status | Published - 2010 Nov 16 |
Bibliographical note
Funding Information:This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) ( R11-2005-017-05001-0 ) awarded to Dr. Kim, and by a research Grant Number 1 RO1 DE013970-01A2 from the National Institute of Dental and Craniofacial Research awarded to Dr. Cohen.
Keywords
- Breast cancer
- Immunity
- Trop-1
- Tumor antigen
- Vaccination
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases