Peter P. Lee, M.D., believes science will find a way to help the immune system conquer breast cancer, but researchers need to rethink their approach to immunotherapy. The U.S. Department of Defense agrees, and it recently gave Lee some major financial backing to make it happen.

Peter Lee’s new grant boosts studies of immunotherapy for breast cancer. (Photo by Darrin S. Joy)

It awarded Lee a five-year, $3.1 million grant, called an Era of Hope Scholar Expansion Award, through its Breast Cancer Research Program. His “Integrated Immunotherapy for Breast Cancer” project earned one of only two grants awarded this year and continues advances Lee made under an earlier $4 million grant. It accelerates Lee’s efforts to develop a holistic approach to stoking the immune system to overcome breast cancer.

He calls it holistic because he believes immunotherapy has to affect all three phases of the body’s immune response to disease — not just one — to work.

Stages of self-defense

The first phase starts after foreign cells like bacteria enter the body, or cancer cells develop within it. Immune system cells called dendritic cells detect these unwanted cells and begin to signal a problem that activates the immune system’s response.

In the second phase, immune cells called T cells start to multiply and spread. These cells mount a defense against the disease-causing cells. As long as the unwanted cells remain, the immune system continues to pump out more T cells.

During the final phase, the T cells seek out and attack the foreign or cancer cells.

According to Lee, who recently joined City of Hope as professor and associate chair of the Department of Cancer Immunotherapeutics and Tumor Immunology, today’s immune-based cancer therapies have limited effect because they concentrate only on one stage of immune response.

Vaccines, for instance, focus on the first phase by delivering a cancer-specific molecule in hopes that the immune system will react and start producing anti-cancer T cells. And immune-boosting drugs address the last phase, aiming to push T cells into a frenzied attack against cancer cells.

Lee believes a truly effective therapy relies on “looking at the whole system.”

“Without doing that,” he said, “you often end up with a therapy that either doesn’t work in clinical trials or that, at best, improves survival by a matter of weeks or months.

“I want to find something that works better, that really has the potential for a lasting cure.”

Three-pronged attack

The Department of Defense grant builds on his earlier work. Previously, Lee and his colleagues found that dendritic cells work better when they group together. They also found that cancer patients’ dendritic cells do not cluster as well as those in healthy patients.

“We’ll try to find out how cancer blocks dendritic-cell clustering and overcome it, and we’ll also try using methods we know already promote clustering” to see if they can improve a vaccine’s effectiveness, said Lee.

“But this is only part of the combination therapy,” he added.

His team also found that cancer seems to affect how immune cells communicate. Immune cells use biochemical signals to coordinate an attack on cancer, but signals become garbled in breast cancer patients. This often means not enough T cells emerge to fight the cancer. Lee hopes to better understand the signaling and fix it in cancer patients.

Ultimately, Lee aims to have a new combination treatment ready for clinical trials within five years.

“I came here because I want to translate discoveries to patients. I see City of Hope as an excellent place to do that, with its unique clinical resources and manufacturing facilities.

“With these resources and using our combined approach, I’m confident we’ll have a much more effective treatment down the road. I look forward to working with many outstanding colleagues at City of Hope to develop these therapies.”

Lee joined City of Hope after 17 years at Stanford University School of Medicine and Stanford Cancer Institute in November 2011.