Researchers have found a new way to boost the immune system's anti-tumor activity and shown it is safe in mice. They believe their findings will lead to new drugs that target the protein involved so the immune system shrinks tumors without affecting healthy tissue.
Dr. Wayne Hancock of the division of transplant immunology at The Children's Hospital of Philadelphia, and colleagues report their findings in this week's online issue of Nature Medicine.
The study focuses on a question that fascinates immunologists: why doesn't the immune system prevent cancer in the first place? It has the tools to do so.
In a statement, Dr. Hancock explains how the answer to this question is not simple.
It requires us to understand the delicate balance the immune system must strike among its various elements to attack disease without triggering dangerous, even life-threatening assaults on healthy cells.
In the new study, the researchers examined a group of immune cells called T regulatory (Treg) cells. Previous studies have shown these cells are important for suppressing immune activity and can block the immune system's ability to attack cancer.
However, attempts to reduce these cells as a way to boost immune attacks on cancer cells have not been very successful.Dr. Hancock says:
"We needed to find a way to reduce Treg function in a way that permits antitumor activity without allowing autoimmune reactions."
Their discovery came when they worked on a subset of cells called Foxp3+ Tregs. It appears there is a way to reduce tumor growth without promoting autoimmunity if you target a Treg enzyme called p300.
The protein Foxp3 plays a key role in controlling how Tregs behave, and p300 is the trigger. By deleting the gene that expresses p300, the researchers found Treg cells safely limited tumor growth in mice.
They also found that a drug known to block p300 in normal mice has the same effect.
The team now plans to look more closely at how to target p300 as a new immunotherapy against cancer.
Dr. Hancock describes the study as a preclinical "proof of principle," with potential for translation into the clinic. He says drug companies have already expressed an interest.
The study, which investigates how to reduce Treg activity, is the flip side of earlier work by the team where they sought to increase Treg activity in order to increase the body's tolerance after organ transplant.
In both cases, he and his team used groups of chemicals called cetyl groups to change the behavior of Treg cells, in opposite directions.
"This is the yin and yang of immune function," Dr. Hancock says.
Funds from the National Institutes of Health helped finance the research.Written by Catharine Paddock PhD