Blocking Blood Supply to Breast Carcinoma with a DNA Vaccine Encoding VEGF Receptor-2
Abstract
Proof of concept was established for the hypothesis driving this project indicating that effective suppression of tumor angiogenesis can be achieved with a DNA vaccine encoding murine VEGF receptor-2 (FLK-l) designed to induce CTL-mediated immune responses by targeting proliferating endothelial cells in the tumor vasculature. This vaccine effectively protected mice from lethal tumor cell challenges and reduced growth of established metastases. CTL-medicated killing of endothelial cells indicated breaking of peripheral immune tolerance against the FLK-l self-antigen resulting in markedly reduced dissemination of metastases. Angiogenesis in the vasculature was suppressed without impairment of fertility, neuromuscular performance or hematopoiesis with only a slight delay in wound healing. In addition we constructed novel minigene-based DNA vaccines encoding multiple FLK-l nonapeptides with either H-2Kd and/or H-2Dd anchor residues. Furthermore, a novel vaccine was developed against the fos-related transcription factor (Fra-l), co-expressing secretory IL-l8, which was highly effective in suppressing or eradicating aggressive breast carcinoma metastases by inducing anti-angiogenesis coupled with pronounced activation of T-and NK cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2003
- Accession Number
- ADA426547
Entities
People
- Rong Xiang
Organizations
- Scripps Research