A Novel Gene Gun-Mediated IL-12 Gene Therapy for Breast Cancer
Abstract
Advanced breast cancer is highly metastatic, and no methods exist to prevent relapse. Animal studies suggested that immunotherapy might achieve regression of both primary tumors and metastases and induce immunological memory to prevent recurrence. Unfortunately, many patients experienced toxicity from high systemic cytokine doses. In hopes of reducing toxicity, we and others tested localized cytokine administration via gene transfer. Using a gene gun to deliver interleukin 12 (IL-12) cDNA to the skin over a tumor site, we achieved partial to complete regression and anti metastatically effects in six non-breast mouse tumor models, without apparent toxicity. We are now testing these protocols in two mouse models of mammary adenocarcinoma. In the moderately immunogenic TS/A model, we achieved complete regression in 50% of mice. Those mice remained tumor free for an extended period, resisted secondary tumor challenge, and displayed augmented cell mediated cytotoxicity, thus demonstrating immunological memory. In contrast, for the non-immunogenic 4T1 tumor, primary tumor growth was not affected by IL-12 gene therapy, although lung metastasis was significantly reduced. The anti metastatically effect in the 4T1 model appears to be T cell independent, and we are investigating its mechanism. These results suggest that a similar gene therapy protocol may be useful in human breast cancer treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA336811
Entities
People
- Ning-sun Yang