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Using antibodies from camels and alpacas, scientists at Washington University School of Medicine in St. Louis have found a way to deliver anticancer viruses directly to tumor cells, leaving other types of cells uninfected.The research appears Feb. 18 in Molecular Therapy—Oncolytics.
The scientists showed that unlike human antibodies or those of most other animals, the antibodies of camels and alpacas survive the harsh environment inside cells and retain the ability to seek out targets, potentially solving a longstanding problem in the field of gene therapy.“For decades, investigators have been putting human or mouse antibodies on viruses, and they haven’t worked — the antibodies would lose their targeting ability,” said senior author David T. Curiel, MD, PHD, distinguished professor of radiation oncology. “It was a technical problem. During replication, the virus is made in one part of the cell, and the antibody is made in another. To incorporate the two, the antibody is dragged through the internal fluid of the cell. This is a harsh environment for the antibodies, so they unfold and lose their targeting ability.”
Typical antibodies (top) unfold in the harsh environment of the cell. Camelid antibodies (bottom) are smaller and more stable.
Antibodies are proteins of the immune system that travel through the bloodstream and recognize potential threats to the body, whether bacteria, viruses or abnormal cells. Most antibodies have a characteristic Y shape. The tips of the Y form a “lock” that binds to a specific “key” carried by foreign bodies that the immune system should destroy.
According to Curiel, recent work by other groups has identified an unusually small and stable class of antibodies made by camels, alpacas and related species collectively classified as camelids. The “lock” of camelid antibodies consists of the stem of the Y only, so it can’t unfold in the harsh internal environment of the cell.
“We found that when we incorporated the camelid antibodies into the virus