Gene Therapy Shrinks Tumors, Boosts Immune System

Utilizing an innovative gene-based therapy before breast cancer surgery typically reduced tumor size by almost 80%, according to a new report.

The therapy, known as Advexin, also demonstrated that the p53 protein it was delivering was being replaced in the targeted tumors, and that the treatment provided beneficial and perhaps continued local immune responses in the patients given the treatment. Advexin was developed by Introgen (Austin, TX, USA).

"We have nice evidence of a double-acting mechanism of gene therapy, something that has not been seen before in patients treated with only chemotherapy,” observed Massimo Cristofanilli, M.D., associate professor in the department of breast medical oncology at the University of Texas M.D. Anderson Cancer Center (Houston, TX, USA). Approximately 50% of patients with locally advanced breast cancer have mutations in their p53 gene, which plays an important role in suppressing tumor development. The gene therapy uses an adenovirus vector to supply normal p53 genes in very high concentrations to tumor cells.

In the study, 12 patients with locally advanced breast cancer, each of whom had large tumors (a median of 8 cm), received several injections of Advexin directly into the tumor, followed by a course of chemotherapy. The combined therapy resulted in considerably smaller tumors--all reduced by more than 50% to a median size of 1.78 cm--which meant that many of the patients could choose lumpectomy instead of mastectomy. Tumors in patients' lymph nodes also reduced in size.

After tumor removal, scientists examined the tissue and discovered that all of the specimens demonstrated extensive infiltration of T-lymphocytes, which are components of the immune system known to fight cancer cells, as well as higher levels of healthy p53 mRNA, suggesting that there may be an increase in the p53 protein, which protects again cancer development and progression.

Twenty months after surgery, tumors returned in two of 12 patients, and one had died from the disease. "This is a better response than is typically seen in most patients with locally advanced breast cancer," said Dr. Cristofanilli. He said, however, that additional research is planned, including comparative studies of Advexin and chemotherapy.




Related Links:
University of Texas M.D. Anderson Cancer Center