Novel Approach Developed On Antitumor Immunotherapy

Researchers at the Children's Hospital of Philadelphia (CHOP) believe they have found a new approach to stimulating the body's immune system to attack tumors. The work, performed in animals, is not ready for clinical use in humans. However, the technique, which makes use of a key protein to control immune function, lends itself to further study using candidate drugs that employ the same mechanisms, say the scientists.

"This preclinical study demonstrates proof of principle that using a drug to regulate the function of a special, immunosuppressive subset of so-called T-regulatory (Treg) cells safely controls tumor growth," explains study leader Wayne W. Hancock, M.D., Ph.D., of the division of transplant immunology at CHOP. "It really moves the field along toward a potentially major, new cancer immunotherapy."

Dr. Hancock and colleagues published the study today in Nature Medicine.

"There's a basic paradox in immunology: why doesn't the immune system prevent cancer in the first place?" continues Dr. Hancock. The answer is complicated, he adds, but much of it involves a delicate balancing act among elements of the immune system. While immunity protects us against disease, an overly aggressive immune response may trigger dangerous, even life-threatening, autoimmune reactions in which the body attacks itself.

In the current study, Dr. Hancock focused on Foxp3+ Tregs. Investigators already knew that Tregs were known to limit autoimmunity, but often at the cost of curtailing immune responses against tumors. "We needed to find a way to reduce Treg function in a way that permits antitumor activity without allowing autoimmune reactions," said Dr. Hancock.

His group showed that inhibiting the enzyme p300 can affect the functions of another protein, Foxp3, which plays a key role in controlling the biology of Tregs. By deleting the gene that expresses p300, the researchers safely reduced Treg function and limited tumor growth in mice. Notably, they also achieved the same effects on p300 and Tregs in mice by using a drug that inhibits p300 in normal mice.

Dr. Hancock will pursue further investigations into targeting p300 in immunotherapy.