Delivering a targeted immunotoxin into breast ducts via openings in the nipple wiped out all visible and invisible precancerous lesions in laboratory studies, led by researchers at the Johns Hopkins Kimmel Cancer Center, of very early stage breast cancers.
A description of the work performed on mice, which the authors say provides a strong pre-clinical foundation for conducting feasibility and safety trials with patients who have stage 0 breast cancers, is published in the June 8 issue of the Proceedings of the National Academy of Sciences.
Stage 0 breast cancer, also known as ductal carcinoma in situ (DCIS), is characterized as the presence of abnormal, precancerous cells inside milk ducts in the breast, and it affects about 69,000 women each year in the United States. Many women have breast removal surgery and radiation treatments for these very early cancers, and in some cases, they receive chemotherapy or hormone therapies, says senior study author Saraswati Sukumar, Ph.D., a Johns Hopkins professor of oncology and pathology.
“In our research, we proposed an alternative treatment in which injecting the immunotoxin drug through the duct could result in cleaning out the DCIS,” says Sukumar. “To our big surprise, the drugs killed every single lesion present in that breast duct. I had never seen such dramatic results in my life.”
During their investigations, the researchers first assessed the cell-killing effects of HB21(Fv)-PE40, a targeted immunotoxin, in four cell lines of different molecular subtypes of breast cancer. The toxin consists of HB21, a monoclonal antibody — a protein that can bind to a specific target (in this case, to the human transferrin receptor, a carrier protein found in breast cancers). HB21 is fused to PE40, a fragment of a bacterial toxin that halts protein production in the cells and leads to cell death. Results showed that the treatment induced strong cancer-killing effects in all cell lines. The researchers also administered the treatment to about 10 mice to look for toxins circulating in the blood after treatment, and found no toxins five to 30 minutes after injection.
Next, they injected HB21(Fv)-PE40 into the breast ducts of two mouse models of DCIS: MCF7 and SUM225. In MCF7 mice, the treatment was given once per week for three weeks. Treatments were followed up with noninvasive imaging. To compare, they also administered the treatment into the body and delivered the HB21 antibody alone into the ducts in some of the mice. The two models represented all of the classifications for common types of human breast cancers: estrogen and progesterone receptor-positive and human epidermal growth factor receptor 2 (HER2) negative, estrogen and progesterone receptor-negative and HER2-positive.
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