Targeting Radiation Therapy for Developing Dendritic Cell Based Immunotherapy of Metastatic Prostate Cancer
Abstract
In this proposal the effectiveness of developing a novel immunotherapeutic strategy following Radiotherapy for prostate cancer has been explored. The hypothesis was tested using a murine prostate cancer model, RM-1. The study showed that irradiation induces apoptosis and the irradiated tumor cells were able to activate dendritic cells and stimulate tumor specific immune response in vitro. In vivo immunization of animals with activated DCs was able to increase their survival against subsequent challenge with tumor cells. Treatment with CCL-21 following DC expansion by FL+IL-12 in animals bearing irradiated tumor, significantly increased their survival time when they were challenged with tumor cells. This regimen also generated a tumor specific immune response as evidenced by in vitro studies. Similar protection was observed when CD40L was used instead of CCL-21 following treatment with FL+IL-12. The study further showed that the administration of adenovirus (Ad-CCL-21) to prostate tumor bearing animals significantly increased their survival time. Collectively, our study provides anovel approach to treat advanced prostate cancer patients following radiotherapy. Aprotocol for treating prostate cancer patients undergoing radiotherapy could be developed immediately based on these findings.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2006
- Accession Number
- ADA475161
Entities
People
- Prabir K. Chakravarty
Organizations
- Albert Einstein College of Medicine