Research scientists develop bioengineered treatment for targeting pancreatic cancer

Research scientists from Massachusetts General Hospital, Boston, have developed a novel bioengineered treatment that has shown promise in targeting pancreatic cancer without causing damage to healthy noncancer cells, a typical problem of chemotherapy. They presented their findings at the 95th annual Clinical Congress of the American College of Surgeons.

According to author Claudius Conrad, MD, PhD, the bioengineered construct used in the treatment is made of engineered, bone marrow-derived mesenchymal stem cells and a gene product toxic to tumor growth that is expressed when the tumor actively recruits the stem cells.

Pancreatic cancer is a highly fatal disease. Approximately 43,000 new cases are diag-nosed each year in the United States, and 35,000 people die from the disease, according to the National Cancer Institute. "The prognosis of advanced pancreatic cancer is so devastating that even a small effect on prolongation and quality of life would be tremendous outcome for
the patient," Dr. Conrad said.

Cancer cells need stem cells to sustain their rapid growth. The bioengineered construct, which the researchers named "Trojan Horse" mesenchymal stem cells, confuses the cancer cell to actively recruit it and then proceeds to produce a potent toxic gene product by using signals that tumor sends to supply itself with new blood vessels.

The side effects of chemotherapy for pancreatic cancer include bowel damage, hair loss, diarrhea, and nausea. "Chemotherapy targets all fast-dividing cells, destroys or inhibits metabolites needed to make DNA and RNA or other vital substrates, disrupts chromosomes, and doesn't care where the dividing cell is," Dr. Conrad said. "We developed our concept of using stem cells to target tumor cells because the homing drive of aggressive tumors like pan-creatic cancer is so strong that genetically engineered stem cells can help destroy the tumor. Also, the unique signals in the tumor microenvironment can help make the therapy cancer-specific once the modified stem cells have been homed."

This latest finding is still in the early stages of development, having been tested in labor-atory animals. However, the results are promising and suggest a way of killing cancer cells with minimal side effects. The Massachusetts General Hospital research team led by Dr. Conrad is working with researchers at Harvard and the University of Munich to develop protocols for further study, which include producing the "Trojan Horse" construct and, eventually, applying for Food and Drug Administration review.