Novel Combination Therapy for Prostate Carcinoma
Abstract
The hypothesis driving this project is that effective blocking of tumor angiogenesis by a DNA vaccine encoding the entire VEGF receptor Flk-l gene induces effective T cell-mediated immunity against proliferating endothelial cells overexpressing Flk-1. This eradicates tumor growth and metastases of RM-2 prostate carcinoma in syngeneic mice. We established that a novel oral DNA vaccine encoding the entire Flk-1 gene successfully suppresses tumor growth and metastases by targeting genetically stable, proliferating endothelial cells in the tumor vasculature rather than mutating tumor cells. This vaccine effectively protected mice from lethal challenges of RM-2 prostate carcinoma cells in a prophylactic model and reduced growth of established metastases in a therapeutic setting. Furthermore, angiogenesis in the tumor vasculature was suppressed without impairment of fertility, neuromuscular performance or hematopoiesis, although with a slight delay in wound healing. We also constructed the first anti-angiogenic Flk-1 minigene vaccine and identified the initial H-2 Db-restricted Flk-1 epitope-FLK((sub 400) (VILINPISM) specifically recognized by CD8+T cells. Importantly, these minigene vaccines achieved similar antitumor efficacy as the DNA vaccine encoding the entire Flk-l gene. Additionally, we elucidated specific CTL-mediated immune mechanisms induced by the Flk-l-based DNA vaccine against RM-2 prostate carcinoma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA435053
Entities
People
- Rong Xiang
Organizations
- Scripps Research