Antibody May Help Treat Breast Cancer

An antibody that targets the blood vessels feeding tumors considerably reduced breast tumor formation and growth in laboratory mice when combined with a cancer drug called docetaxel, according to new research.

"This antibody could enhance the therapeutic efficacy of the drug docetaxel in breast cancer patients,” said Dr. Philip Thorpe, professor of pharmacology at the University of Texas, Southwestern (Dallas, USA) and senior author of the research. "The combination merits further scrutiny as a potential treatment for human cancer.”

Docetaxel is one of the most successful chemotherapeutic agents used for treating breast, prostate, and ovarian cancer, but its use in treating other cancers is restricted by its toxicity. In a study with laboratory mice, the researchers discovered that the antibody compound 3G4 was effective as a vascular targeting agent (VTA) when used with docetaxel. VTAs are designed to search and destroy blood vessels within tumors, cutting off their blood supply.

In particular, mice engineered with human breast tumors treated with 3G4 and docetaxel had a 93% decrease in overall tumor growth. The injected breast cancer cells also triggered the growth of tumor colonies in the lungs, and the drug combo reduced the average number of those colonies by 93%, with 50% of the mice not developing any lung tumors. The combination of 3G4 and docetaxel was much better than either compound used alone, Dr. Thorpe said. In mice with breast cancer tumors, growth was inhibited by 50% using 3G4 alone and 70% for docetaxal alone. The reduction in lung tumor colonies was 82 % with 3G4 alone and 78% with docetaxal alone.

Peregrine Pharmaceuticals (Tustin, CA, USA) is developing a version of 3G4 called Tarvacin for cancer treatment and recently received approval from the U.S. Food and Drug Administration for a phase I clinical trial. The compound was discovered by Dr. Thorpe's lab, and Peregrine has a sponsored research agreement with UT Southwestern to further refine the drug. "We are currently investigating whether the enhanced therapeutic efficacy with 3G4 and docetaxel extends to other tumor models and other conventional therapies,” Dr. Thorpe said.

VTAs such as 3G4 target tumor vessels by selectively binding to a specific component in the membranes of endothelial cells that line tumor blood vessels. This component, called an anionic phospholipid, faces the interior of cells in normal blood vessels. However, in tumor blood vessels, alterations in the tumor environment cause the phospholipid to turn inside out and be positioned on the external surface. VTAs then can attach to this exposed phospholipid, causing the body's white cells to attack and kill the vessels feeding the tumor.

By targeting receptors exclusive to tumor vessels, vascular targeting agents destroy tumors without causing injury to surrounding healthy tissue. They also decrease the risk of side effects by working at lower doses than conventional cancer treatments because they are effective without having to penetrate the innermost layer of a tumor. Whereas drug resistance caused by the instability and mutability of cancer cells is a considerable problem with traditional therapies that target tumor cells, cells targeted by VTAs do not mutate to become drug-resistant, according to Dr. Thorpe. Tarvacin has also shown promise in mice against cancers in the fibrous tissues, Hodgkin's disease, and brain tumors.




Related Links:
University of Texas, Southwestern
Peregrine Pharmaceuticals