A new immunotherapy program at the Mass General Cancer Center is using engineered cells from the human immune system as powerful living drugs.

Since 9th grade biology, Marcela Maus, MD, PhD, has dreamed of fixing genes gone wrong and curing diseases like cancer. These days, as director of the Mass General Cancer Center’s new Cellular Immunotherapy Program, she is a rising star in an avenue of immunotherapy research that has the potential to cure some cancers.

Already showing enormous potential in treating blood cancers, so-called CAR T-cell therapy has been found to eliminate the disease in about 90 percent of those with certain kinds of previously untreatable leukemias and lymphomas.

Her research is focused on T cells, a type of white blood cell key to the human immune system. Dr. Maus is exploring how to use them to essentially paint a big X on tumor cells, so they can be targeted and killed.

Already showing enormous potential in treating blood cancers, so-called CAR T-cell therapy has been found to eliminate the disease in about 90 percent of those with certain kinds of previously untreatable leukemias and lymphomas. It has shown promise too for multiple myeloma. Dr. Maus is investigating how variations of the therapy may also be used against other cancers as well.

Cells with Long Memories

“What’s really impressive is that these remissions can last a long time because immune cells have a long memory,” says Dr. Maus. “It’s a powerful, living drug unlike any other.”

The treatment uses T cells removed from a patient’s own blood. Researchers then genetically engineer the cells to express a protein on their surface called a chimeric antigen receptor (CAR), which targets and locks onto a substance on the surface of the tumor. The engineered T cells are returned to the patient’s bloodstream, where they multiply and seek and destroy tumors with that target.

Dr. Maus's research is focused on T cells, a type of white blood cell key to the human immune system.
Dr. Maus’s research is focused on T cells, a type of white blood cell key to the human immune system.

“One infusion of CAR T cells can melt away seven pounds or more of tumor,” Dr. Maus says. “It calibrates its own dose depending on how much tumor there is.”

One Mass General patient, Jenn Gilman, has already benefited from CAR T-cell therapy. After a lymphoma diagnosis in 2011, Jenn and her Mass General oncologist, Jeremy Abramson, MD, tried 11 different treatments including 5 clinical trials, but nothing worked. Eventually, Dr. Abramson referred Jenn to the National Institutions of Health in Maryland for a CAR T-cell therapy clinical trial that ultimately saved her life (watch Jenn’s story). Now, Dr. Maus is bringing this treatment to Mass General and working to make it more accessible to patients by building a production facility and expanding clinical trials.

Excitement about Immunotherapy

Currently, the mainstay treatment for most blood cancers—which include leukemia, lymphoma and multiple myeloma—are the cell-killing chemotherapy drugs that have been used for decades. New drugs targeted to interfere with cancer growth and progression have made a dramatic difference for some blood cancers. “But although we’ve made great strides in the past decade, most blood cancers, with notable exceptions, remain incurable with conventional therapies,” explains Timothy Graubert, MD, director of the Cancer Center’s Hematologic Malignancies Program. “So there is great excitement about immunotherapy.”

“There is a potential to cure some of these diseases that we’ve been unable to cure, through cellular therapies alone or in combination with other targeted therapies and chemotherapies.”

Mass General Cancer Center launched its Center for Cancer Immunology in 2015, headed by Nir Hacohen, PhD, an immunologist and geneticist. In addition to Dr. Maus’s Cellular Immunotherapy Program, there are also efforts underway at the center to develop vaccines and “checkpoint inhibitor” drugs to unleash immune system responses that tumors have deviously stopped. Immunotherapy complements the pioneering work in targeted therapies underway at Mass General’s Henri and Belinda Termeer Center for Targeted Therapies.

Mass General researchers are gearing up to enroll patients in seven new clinical trials testing variations of CAR T-cell therapy for different kinds of cancers. “There is a potential to cure some of these diseases that we’ve been unable to cure, through cellular therapies alone or in combination with other targeted therapies and chemotherapies,” Dr. Graubert says. “We’re very excited to bring these therapies to our patients.”

Discovering New Targets


MGH patient Jenn Gilmann (above, left) has already benefitted from immunotherapy. Watch her amazing story.

That is certainly Dr. Maus’s hope. But many research challenges remain, particularly in adapting T-cell therapy to target solid tumors. In her laboratory, “We’re discovering new targets on the tumor cells of different diseases and trying to improve the targets we already have to make the therapy safer and more effective,” she explains.

Dr. Maus and her colleagues reported last year, for example, finding a new tumor target for CAR T-cell therapy that is expressed in certain patients with a deadly brain cancer called glioblastoma. They then engineered T cells to seek and destroy cells with that target. It is now being tested in early clinical trials.

Dr. Maus and hospital leaders are raising funds to build and equip a Mass General facility where she and others can make and test such cell-based therapeutics. Because cells are taken from and returned to patients, these sophisticated facilities must satisfy strict government regulations, “good manufacturing practices,” designed to keep the environment free of contamination.

Traditionally, pharmaceutical companies manufacture drugs. “But with T-cell therapy we’re using the immune system itself as a drug,” she says. With one of these facilities, “we can make our own cell products.”

Not Wanting to Wait

Though expensive, not having a facility means “you have to either wait until the company producing them sponsors a trial or until the FDA approves them,” Dr. Maus adds.

Building such a facility will be no small feat. It will require as much as 11,000 square feet with separate culture rooms to make each product one at a time—be it a cell or a protein like an antibody. Quality control testing will be done in other rooms to ensure sterility and potency. It will be equipped with state-of-art bioreactors, incubators, centrifuges and cell and particle counters, and staffed by highly-trained technicians and specialists.

Though expensive, not having a facility means “you have to either wait until the company producing them sponsors a trial or until the FDA approves them,” she adds.
Given some of the dramatic and enduring responses to T-cell therapies, Mass General researchers like Dr. Maus don’t want to wait. There are patients, many of whom have run out of options, who are depending on the swift translation of the researchers’ most promising ideas into new therapies.

For more information about how you can support Dr. Maus’s research, please contact us.