Blocking Blood Supply to Breast Carcinoma with a DNA Vaccine Encoding VEGF Receptor-2
Annual rept. 15 Mar 2002-14 Mar 2003
SCRIPPS RESEARCH INST LA JOLLA CA
Pagination or Media Count:
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 andor 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.
- Anatomy and Physiology
- Medicine and Medical Research