Blocking Blood Supply to Breast Carcinoma With a DNA Vaccine Encoding VEGF Receptor-2
Abstract
Our major tasks in this last grant year focused on gaining insights into CTL-mediated immune mechanisms induced by FLK-1 whole gene and minigene-based DNA vaccines against breast tumors. We also extended our efforts to a new area of breast cancer research by targeting the transcription factor Fos-related antigen 1(Fra-1), overexpressed by breast carcinoma. As mentioned in last year's progress report, we extended the last grant period by one more year because of these additional exciting and novel findings. We report for the first time on the anti-breast carcinoma activity of antiangiogenic DNA minigene vaccines and identify the first H-2 Db-restricted FLK-1 epitope-FLK400 (VILTNPISM). Importantly, the pHI-Db and pHI-FLK400 minigene vaccines achieved similar efficacy as the DNA vaccine encoding the full length FLK-1 gene. They present a much simpler and more manipulatable alternative to the whole gene vaccine and add a new dimension to anti-angiogenic interventions in breast cancer. In addition, we also demonstrated that immunization with a DNA vaccine encoding murine Fra-I, co-transformed with a gene encoding secretory murine cytokine IL-i 8, can effectively eradicate two different breast cancers, 4T1 and D2F2 in syngeneic mouse models and generate a long-lived specific tumor-protective immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA435113
Entities
People
- Rong Xiang
Organizations
- Scripps Research