Stem cells ferry concentrated anticancer drug to tumors

WASHINGTON (AP) _ Texas researchers say they have perfected a method to deliver cancer treatment directly into tumors, bypassing healthy tissue. <br/><br/>The study was done on mice, but human trials could

Tuesday, November 2nd 2004, 4:06 pm

By: News On 6

WASHINGTON (AP) _ Texas researchers say they have perfected a method to deliver cancer treatment directly into tumors, bypassing healthy tissue.

The study was done on mice, but human trials could begin soon, said Dr. Michael Andreeff, one author of the study in Wednesday's issue of the Journal of the National Cancer Institute.

The research team used the benefits of a known anticancer therapy, interferon beta, that can kill cancer cells. In practice, that therapy has proven problematic. It causes toxic side effects and its benefits disappear within minutes of patients getting their shots.

The research team worked around those problems by manipulating a certain type of stem cells to encode the interferon beta gene. The stem cells then move like guided missiles, targeting tumor cells and producing high concentrations of therapeutic proteins within the tumor cells, Andreeff said.

Besides taming toxic side effects, the cancer treatment stuck around in the tumor longer, he said in an interview.

Mice with human breast cancer treated with the engineered human stem cells survived for 60 days, according to the JNCI paper. Mice treated with interferon beta alone lived for 41 days. Untreated mice survived for 37 days. Meanwhile, mice with melanoma treated with the stem cells survived 73.5 days, compared with 30 days for untreated mice.

Andreeff said he's working on a protocol for a clinical trial to test the procedure in humans within a year, if the Food and Drug Administration agrees. Patients would be infused with the stem-cell-delivered anticancer treatment four times a week, said Andreeff, a professor in the departments of blood and marrow transplantation and leukemia at the University of Texas M.D. Anderson Cancer Center.

The targeted delivery of anticancer therapy to tumors builds on what researchers already know about how wounds heal.

The specialized stem cells _ known as mesenchymal stem cells _ come from bone marrow and help maintain healthy connective tissues. When new tissue is needed to heal wounds or form scars, those special stem cells swell in number.

Even though they're tumors, the malignant cells act just like ``never-healing wounds,'' Andreeff said. Half the tumor is made up of stomal cells that provide structural support. For the body, forming that tumor support structure is much like healing wounds and forming scars.

Enter the specialized stem cells. Giving them the clues they need to take on the construction duties of stomal cells delivers the cancer-busting ability directly to tumors.

Andreeff's research team did not see engineered stem cells drift into healthy organs like the lungs, liver, spleen, kidney or muscles.

But because the stem cells are driven by a duty to help, that means a wound elsewhere in the body could distract some from reaching tumors.

``Any wound that's active, that requires repair, would be a target,'' Andreeff acknowledged. That means doctors would need to screen patients carefully to ensure the therapy is not attempted on people who had undergone recent surgery, for example.

The work builds on the promise of using stem cells to hunt down brain tumors, outlined in a 2000 paper in the Proceedings of the National Academy of Science.

``It was my hope that other investigators looking at other areas, using other stem cells ... would seize upon this,'' said Dr. Evan Snyder, director of the Burnham Institute's stem cell program in La Jolla, Calif., and an author of the earlier paper. Snyder called the JNCI article ``important, because it's proof of concept.... In this case, a mouse is simply a surrogate for a human being.''