Adenoviral Mediated Interleudkin-12 Gene Therapy for Metastatic Breast Cancer

摘要

Our preclinical studies in tumor-bearing mice have shown that intratumoral injection of an adenoviral vector expressing interleukin-12 was effective in inducing tumor regression, antitumor immune responses and long term survival without disease relapse in 40% treated animals. Based on these findings, we have developed a Phase I trial of intratumoral delivery of an adenoviral vector (Adv.RSV-hIL12, ADV-hIL12) expressing the human interleukin- 12 cDNA in patients with metastatic breast cancer to the liver. We have completed preclinical efficacy and toxicity studies to support an IND application to the FDA to conduct the proposed clinical trial. Revisions to the clinical protocol and consent have been made on the recommendations of the FDA and NIH-OBA. We have successfully completed clinical grade production of the study agent (Adv.RSV-hIL12) in the Vector GMP Facility at Mount Sinai. The IND was approved by the FDA (6/11/02). The revised protocol and consent was submitted to the Department of the Army (6/17/02) for approval. The Human Subjects Protection Division of the Department has granted approval on 10/17/04 after further revisions were made at their request. The clinical trial will be activated for patient accrual once the revisions requested by the HSPD have been approved by the local IRB.