"HIV knows how to insert itself into many different types of cells," says senior author William Hawkins, MD.  "A portion of the HIV protein called Tat can transport biologically active compounds into cells. Tat is small, but it can move massive molecules. You could almost hook Tat up to a train, and Tat would drag it inside a cell. So we've taken advantage of this ability."

While the new research may not have direct implications for those living with HIV infection, it illustrates that ongoing HIV research plays a significant role in the development of therapeutics for a variety of human diseases.   

In the article, Dr. Hawkins and his colleagues describe using Tat to pull a protein called Bim into cancer cells. Tat alone cannot cause HIV infection or immune suppression and is not believed to have any adverse health effects. Bim acts as a tumor suppressor and causes cancer cells to die through apoptosis, a process by which cells "commit suicide."

The research team found that the Tat-Bim compound activated apoptosis mechanisms in cancer cells and augmented the cell-killing effect of radiation. When mice with malignant tumors were treated with Tat-Bim, their tumors shrank, and they survived longer than mice that didn't get the treatment. After 40 days, 80% of mice receiving Tat-Bim were alive compared to 20% of mice that didn't get the treatment.

"Unlike most healthy cells, cancer cells grow very fast. So they are always on the verge of running out of natural ingredients like sugars, and mistakes are accumulating in their DNA," Dr. Hawkins says. "This results in signals telling cancer cells to die, but the cells don't quite have the permission they need to do it. Proteins like Tat-Bim can tip the balance in favor of death."

Dr. Hawkins asserts that this success marks the beginning of a very promising new approach to cancer therapy. "This is the tip of the iceberg," he says. "Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die."

To further enhance the cancer-killing power of Tat-Bim and similar proteins under development, Hawkins and his colleagues are working on a technique that will concentrate them within tumors while sparing healthy cells. In collaboration with Robert H. Mach, PhD, Professor of Radiology, they are linking the anti-cancer proteins to tracer molecules that selectively bind to cancer cells.

"Dr. Mach designed tracers to visualize cancer in positron emission tomography (PET) scans," Hawkins says. "By binding our molecules to the tracers, we can deliver them to cancer cells. We've seen phenomenal results in the lab."

Next Hawkins plans to combine pro-apoptotic proteins such as Tat-Bim with chemotherapy, radiation therapy and other anticancer therapeutics in hopes of further increasing cell-suicide signals within cancer cells.

Dr. Hawkins says he thinks treatments that activate apoptosis mechanisms could provide new options for patients with cancers associated with very low rates of survival. While Tat-Bim has not been tested in any humans to date, he says that clinical trials could be just a few years away.

Source:

Kashiwagi H, McDunn JE, Goedegebuure PS, et al. TAT-Bim induces extensive apoptosis in cancer cells. Ann Surg Oncol. Published online: January 6, 2007.