Cell Therapy May Counter Effect of Radiation Damage

By BETSY MASON

WALNUT CREEK, Calif. – Stem cells may soon play a role in the U.S. campaign to be better prepared for a terrorist attack. A Bay Area biotech company is working on a cell therapy that could be used to help victims survive exposure to radiation from an attack or accident.

The technique could also help patients recover from chemotherapy or radiation treatments for cancer or bone marrow transplants, said Janice “Wes” Brown, a Stanford University infectious disease specialist who pioneered the cell therapy and is working to develop it with San Carlos, Calif.-based Cellerant Therapeutics Inc.

The aim is to create an easily administered treatment that can be stockpiled for future emergencies, a goal they hope to reach by 2008.

Chemotherapy and radiation help fight cancer cells, but also leave patients with a weakened immune system for several weeks, which opens them up to potentially life-threatening infections. Currently the only help doctors can offer is broad spectrum antibiotic and antifungal drugs that aren’t 100 percent effective against potential infections and bring their own problems with toxicity and side effects.

“And the most important thing is that once they develop an infection, they can die from that infection,” said Brown.

Three types of blood cells are injured by radiation. Platelets and red blood cells can be replaced, but white blood cells are problematic. In particular, a type of white blood cell known as a neutrophil, which is critical to the immune system, doesn’t live long outside of the body. Even under the best circumstances, with a rapid blood transfusion, the majority of these neutrophils die before they can help patients fight off infections.

In hopes of finding a better alternative for her patients, Brown followed up on ground-breaking research by Stanford stem cell pioneer, Irving Weissman, who discovered the adult stem cells in the bone marrow that give rise to all types of blood cells. Weissman later isolated “progenitor cells” that exist partway down the path from stem cells to several types of blood cells, including the fragile neutrophils.

Brown led a research team at Stanford that studied progenitor cells by injecting them into the bloodstream of mice exposed to radiation. She found the progenitors were able to produce neutrophils after a few days.

“We can cure mice with a lethal exposure to radiation,” said R.J. Tesi, vice president of medical affairs and clinical development for Cellerant.

The mice that received the cell treatment were able to fend off a potentially fatal fungal infection that commonly attacks chemotherapy patients.

The progenitor cells and the blood cells they spawn live for about 35 to 40 days, which gives the mouse’s immune system a chance to recover from the radiation and start producing its own blood cells, including the all-important neutrophils.

“It’s basically this race between them dying of infection and their bone marrow recovering,” Tesi said. “We actually put the race in their favor because we give them something that speeds up their immune system recovery.”

The limited life span of the transplanted cells is an advantage because there are no permanent foreign cells introduced into the patient’s body, which reduces the likelihood of later complications. And unlike bone marrow transplants, progenitor cells do not need to be matched to the patient.

Another huge advantage of progenitor cells is that unlike neutrophils, they can survive outside the body and can even be frozen and stored.

This is particularly attractive for dealing with victims of a radiological attack or accident. A single blood donation will likely generate between 20 and 40 teaspoon-size doses of progenitor cells, which can be stockpiled. And the process for giving the cells to patients will be relatively straightforward e basically transfusing the cells into a patient’s bloodstream through an IV e and will take only about 30 minutes.

“We think we’ve found the perfect solution,” said Tesi. “It’s a very attractive scenario for treating a lot of people in a hurry.”

Most of what is known about the effects of radiation exposure, known as “radiation syndrome,” comes from what happened to the victims of Chernobyl and from U.S. government research after the Manhattan Project in the 1940s.

Acute radiation syndrome can affect three different systems: the central nervous system, the gastrointestinal system and the immune system. People who receive enough radiation to suffer central nervous system damage are not likely to survive. Gastrointestinal issues are not often life threatening.

But a large number of people will have potentially lethal damage to their bone marrow and consequently a weakened immune system. Brown and Tesi think their cell therapy can save these people.

Cellerant’s efforts are being supported by the National Institutes of Health to the tune of about $1 million. But the bulk of the research, several million dollars’ worth so far, has been funded by private investors. The potential for saving radiological attack victims has the Department of Homeland Security interested as well.

The large numbers of patients who might benefit from the progenitor cell therapy has helped Cellerant attract investors. About 25,000 people worldwide receive radiation with a bone marrow transplant each year. And around 12,000 U.S. adults are diagnosed with acute myelogenous leukemia each year. Patients with lymphoma and other types of cancer may benefit as well.

Tesi hopes clinical trials to test the therapy in humans undergoing radiation treatment for leukemia, bone marrow transplants and lymphoma will begin next year. If all goes well, the treatment could be available by 2008.