By carefully adjusting the function of crucial immune cells, Children’s Hospital investigators may have developed a completely new type of cancer immunotherapy, one that involves harnessing the body’s immune system to attack tumors.
To accomplish this, the investigators had to thread a needle in immune function, shrinking tumors without triggering unwanted autoimmune responses. At play is 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.
The new research, performed in animals, is not ready for clinical use in humans. However, the approach by Wayne W. Hancock, MD, PhD, and his team makes use of a key protein to control immune function, lends itself to further study using candidate drugs that employ the same mechanisms.
Dr. Hancock, the chief of the Division of Transplant Immunology at Children’s Hospital, focused on a subtype of immune cells called Foxp3+ T regulatory cells, or Tregs. Tregs were already 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,” Dr. Hancock said.
The investigators showed that inhibiting an enzyme called 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, Dr. Hancock and his team 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 plans to pursue further investigations into targeting p300 in immunotherapy. The preclinical findings offer encouraging potential for being translated into the clinic, said Dr. Hancock, who added that pharmaceutical companies have expressed interest in researching this approach as a possible cancer therapy.
“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,” said Dr. Hancock. “It really moves the field along towards a potentially major, new cancer immunotherapy.”