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Novel p53 gene-based therapy boosts immune system and reduces tumor size

SAN ANTONIO - Use of a novel gene-based therapy before breast cancer surgery reduced tumor size by nearly 80 percent on average, researchers from The University of Texas M. D. Anderson Cancer Center report at the annual San Antonio Breast Cancer Symposium meeting.

The therapy, known as Advexin, also showed evidence that the p53 protein it was delivering was actually being replaced in the targeted tumors, and that the treatment produced beneficial and possibly sustained local immune responses in the patients tested.

"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," says Massimo Cristofanilli, M.D., an associate professor in the Department of Breast Medical Oncology. About half of patients with locally advanced breast cancer have mutations in their p53 gene, which plays a critical role in suppressing cancer development. The Advexin therapy uses an adenovirus vector to supply normal p53 genes in very high concentrations to cancer cells.

In the study, 12 eligible patients with locally advanced breast cancer, each of whom had large tumors (an average of eight centimeters, larger than a silver dollar), received several injections of Advexin directly into the tumor, followed by a course of chemotherapy. The combination therapy resulted in significantly smaller tumors - all shrunk by more than 50 percent to a mean size of 1.78 centimeters - which meant that many of the patients could choose lumpectomy (removal only of the tumor) instead of mastectomy (removal of the breast). Tumors in patients' lymph nodes also decreased in size.

After surgery, researchers examined the excised tumors and found all of the specimens showed extensive infiltration of T-lymphocytes, which are components of the immune system known to be involved in fighting cancer cells, as well as higher levels of normal p53 mRNA, suggesting that there may be an increase
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8-Dec-2004


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