The Center for Cancer Immunology’s investigators are working to expand the use of immunotherapy, a revolutionary approach to cancer therapy.

Immunotherapy is the next step on the road to cure cancer, says Nir Hacohen, PhD, director of the Center for Cancer Immunology at Mass General Cancer Center. “Cancer treatment has entered a new era,” he says, “the era of immunotherapy.”

The center's investigators include, from left, Nir Hacohen, PhD; Marcela Maus, MD, PhD; Shawn Demehri, MD, PhD, and Mark Cobbold, MD, PhD.
The center’s investigators include, from left, Nir Hacohen, PhD; Marcela Maus, MD, PhD; Shawn Demehri, MD, PhD, and Mark Cobbold, MD, PhD.

Immunotherapy taps our immune system’s ability to fend off infections that cause diseases. The immune system recognizes viruses and bacteria as being foreign invaders. “But tumors are our own cells that have been transformed,” Dr. Hacohen explains. Some people’s immune systems are able to recognize a tumor as a threat and launch an attack. But others don’t.

Scientists at the Center for Cancer Immunology are studying ways to help everyone’s immune system recognize and destroy a tumor. As their understanding of the complex genetics deepens, they want to use their discoveries to develop new treatments for patients as quickly and safely as possible.

The center is building on the pioneering success of targeted cancer therapies in the Henri and Belinda Termeer Center for Targeted Therapies at the Mass General Cancer Center. In the past decade, breakthroughs in targeted therapies—drugs targeted to attack specific molecules involved in cancer growth—have extended the lives of patients with melanoma, lung, breast and other cancers.

“We’re trying to create more success like that with immunotherapies,” Dr. Hacohen says. But one targeted drug alone is often not enough. Immunotherapy drugs alone, in combination with each other, or in combination with targeted therapy, may be the answer.

Investing funds in cancer therapy is always useful. “But there are moments when things are working so well that investments are more likely to move the field forward fast,”  Dr. Hacohen says. “And this is one of those times.”

The Center for Cancer Immunology is focused on four major approaches to immunotherapy—checkpoint inhibitors, CAR T-cell therapy, vaccine therapy and early cancer immunotherapy.

First Immunotherapy Drugs

Checkpoint inhibitors were the first immunotherapy drugs. To spread, tumors find ways to put the brakes on the body’s immune response at key times. Checkpoint inhibitor drugs are designed to find those checkpoints and release the brakes, re-awakening sleeping immune cells.

“The great success of checkpoint therapy in melanoma triggered an interest in testing its use for almost every kind of cancer,” Dr. Hacohen says. Many variations of this therapy, using different checkpoints and combinations of them, are in clinical trials at Mass General and elsewhere.

Checkpoint therapy is offering hope to people with an increasing list of aggressive cancers, including melanoma, head and neck, kidney, lung and bladder. Baseball Hall of Famer Mike Schmidt benefited from a checkpoint therapy in 2014 when melanoma spread to his lungs. But Dr. Hacohen points out that only about 10-15 percent of patients have long-lasting responses to this therapy. The center’s researchers are determined to pinpoint what makes checkpoint inhibitor therapy succeed or fail and to find ways to extend its benefits.

Using patients’ tumor samples, Dr. Hacohen and his colleagues are analyzing tumor genetics. “We have just found major mechanisms that tumors use to resist immunotherapy,” he reports. That will help predict who will respond to checkpoint therapy and develop ways to override resistance.

In her immunotherapy research, Dr. Maus focuses on T cells, a type of white blood cell key to the human immune system.
In her immunotherapy research, Dr. Maus focuses on T cells, a type of white blood cell key to the human immune system.

Engineering Immune Cells

CAR T-cell immunotherapy is another approach. It involves taking immune system cells called T cells from a patient’s blood and engineering them to target that patient’s tumor. It has produced dramatic, long-lasting successes in certain kinds of leukemias and lymphomas. The center’s Marcela Maus, MD, PhD, is discovering new targets on the tumor cells of different cancers so they can engineer T cells to destroy them too.

The third approach is to design a vaccine to treat an existing cancer by boosting immune system response to it. Dr. Hacohen, in collaboration with his oncologist wife, Catherine Wu, MD, has developed a promising, personalized vaccine that is about to be tested in people with melanoma and glioblastoma, a malignant brain tumor. Whereas vaccines have failed in the past, he believes their approach may succeed.

“We have found what the immune system detects on a tumor,” he says. Called “neoantigens,” these abnormal proteins are produced only by tumors. Patient-specific tumor neoantigens are loaded into a vaccine to stimulate an attack against that patient’s tumor, sparing normal cells.

In his immunotherapy research, Dr. Cobbold has found hundreds of neoantigens that are common to all people.
In his immunotherapy research, Dr. Cobbold has found hundreds of neoantigens that are common to all people.

Another center investigator, Mark Cobbold, MD, PhD, is looking for neoantigens common to all people. He’s found hundreds. That could lead to a vaccine that doesn’t have to be personalized, and that may even be useful in treating early cancers.

Using Immunotherapy Earlier

“Between his work and ours, we are covering all the major neoantigens that the immune system detects,” Dr. Hacohen says. Now they need to figure out which are the best for eliminating a cancer so it doesn’t come back.

Immunotherapy so far has been mainly used for people with advanced cancers. Center researchers also want to see if it can eliminate early-stage cancers. Shawn Demehri, MD, PhD, has found a substance in the immune system that seems to control early development of breast and skin cancer. He’s investigating how this finding in animals can help people.

Dr. Demehri has found a substance in the immune system that seems to control early development of breast and skin cancer.
Dr. Demehri has found a substance in the immune system that seems to control early development of breast and skin cancer.

“It would be fantastic to stop a cancer before it becomes aggressive and dangerous,” Dr. Hacohen says.

Better yet would be a vaccine that prevents cancer. Though a solution is a long ways off, Dr. Hacohen and Dr. Cobbold are pursuing ideas to do that as well.

Opportune Time for Philanthropy

Additional funding for the center and its researchers will let them hire more faculty and create the facilities needed to pursue these exciting research projects. An expanded clinical trial infrastructure is needed to run more trials of novel therapies. Dr. Hacohen would also like to fund collaborative research projects pooling information from patient tumor samples from all Boston hospitals, as well as Harvard and MIT researchers who study tumor immunity, whom he convened at a 2015 cross-institutional retreat.

Investing funds in cancer therapy is always useful. “But there are moments when things are working so well that investments are more likely to move the field forward fast,” he says. “And this is one of those times.”

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