“I am now a GMO. I’m a genetically modified organism, “jokes Dr. Marty Pearlmouth.
Yashik / Arnold, a retired professor of philosophy and honorary director of the Jewish Studies Program at Charleston College, has had the unfortunate opportunity to keep a close eye on advances in medical science – he has been working on various types of cancer for more than a decade. But he is also able to receive the latest treatments, including CAR-T-cell therapy at the MUSC Hollings Cancer Center for his lymphoma.
“In a sense, I no longer have my own blood,” he explained of the treatment. “I have blood that has been modified to fight blood cancer.”
It’s as if science fiction is becoming a reality, he said.
CAR-T therapy is a treatment that is as simple as a concept as well as nuanced in implementation: modernizing existing immune cells to better recognize and fight cancer. Brian Hess, MD, an oncologist who focuses on lymphoma, is leading Perlmutter’s treatment.
“I think it really makes us happy to have this kind of therapy that we can offer to patients,” he said. “If we go back only a few years ago, when these therapies were in a clinical trial and were not approved, these patients had very little or no options otherwise in terms of treating their cancer, and they really didn’t have much hope.”
CAR-T means chimeric antigen receptor T-cell therapy. The therapy has been approved by the Food and Drug Administration for several types of lymphoma, B-cell acute lymphoblastic leukemia and multiple myeloma – but only for patients who have already undergone standard chemotherapy and have relapsed.
Such was the case with Perlmutter, who, after being diagnosed with chronic lymphocytic leukemia, had previously participated in a clinical trial by the National Institutes of Health of ibrutinib, a drug now widely used.
Although Perlmutter initially had good results, the cancer eventually underwent Richter’s transformation, a rare complication in which chronic lymphocytic leukemia transforms into aggressive lymphoma. The initial course of chemotherapy did not work. Hess said it was unlikely that continuing chemotherapy would accomplish anything other than lead to greater toxicity, so he turned to CAR-T.
The treatment requires several steps in about a month. First, the patient’s T cells, which are part of the immune system, are removed in a process called apheresis, which is somewhat similar to blood donation. The difference is that when the blood is collected, the T-cell fraction is separated and the rest of the blood is returned to the patient. From there, the T cells are sent to the laboratory to be modified to express the chimeric antigen receptor or CAR.
“Programming a T cell to express a CAR receptor causes that T cell to target a specific protein on the surface of the cancer cell. In the case of lymphoma, it’s CD19, “Hess said. “In other words, adding CAR to a T cell gives that T cell a specific job, which is to attack the cancer cell that expresses that protein.”
“Adding CAR to a T cell gives that T cell a specific job, which is to attack the cancer cell that expresses that protein.”
Brian Hess, Ph.D.
T cells must come from the individual patient to be treated. This eliminates the chance of T cells starting to attack organs in addition to cancer.
However, serious side effects are still likely. As CAR-T cells continue to multiply in the body, they can sometimes cause things like fever and confusion, Hess said. Some patients had to be admitted, and this was the case with Pearlmouth, who was briefly hospitalized. Nevertheless, the side effects can be managed and reversed, Hess said, and Pearlmutter noted that he quickly returned to normal life.
Two important questions in the field of CAR-T at the moment are how to make CAR-T safer and how to make it more efficient. Reducing side effects and improving the efficacy of CAR-T is the focus of a small clinical trial that will begin later this summer in Hollings.
Based on the work of Dr. Michael Nishimura of Loyola University in Chicago and his colleagues there, the MUSC Cell Therapy Center, led by Shikhar Mehrotra, Ph.D., will produce “purified” CAR-T cells.
The idea, Hess said, is that there are currently other immune system products that infuse patients with CAR-T cells – such as T cells that CAR does not accept, such as other cellular components. – which may increase the risk of side effects. By adding additional follow-up protein to CAR-T, the laboratory will be better able to take only CAR-T cells and infuse only those cells into the patient, which should reduce side effects.
In addition, Mehrotra took the plan from Loyola and changed the way CAR-T cells are activated in a way that the team expects to help CAR-T cells stay longer and be more efficient. Hess praised Mehrotra’s work, noting that the process would not have been possible without his contribution.
Researchers across the country are working to see if CAR-T can be used on solid tumors or can be produced in a standard way.
These goals are a challenge. In solid tumors, the challenge is to find a target that is unique to the cancer so that CAR-T cells also do not cause severe toxicity, Hess said.
“You have to find the right goal, which is really like the Holy Grail for all these other cancers,” he said.
And it is not yet clear whether mass-produced CAR-T cells can be as effective as those obtained from the patient’s own body.
Pearlmouth is eager to see where science will go next.
“For several years I have been saying that I want to be one step behind science. “Treatment has changed so fast in the last 10 years,” he said. “CAR-T is an absolute change in the game. We hope they find a way to treat solid cancers. ”
Perlmutter’s lymphoma went into remission after CAR-T therapy. In fact, his older children organized a one-year CAR-T anniversary party on May 4 to celebrate remission. Hess was there, as were other Hollings suppliers and employees.
Hess said Pearlmouth’s personality was contagious. CAR-T-cell therapy required an entire team to provide care, and the team members who cared for Perlmutter loved to take care of him. They were all sick of him.
“He also has such a wonderful family,” Hess said, pointing to Pearlmouth’s wife, Jerry, whose care was essential after the CAR-T treatment. Pearlmouth called his wife “an extraordinary caregiver who understands the challenges I face as she experiences her own uncertainty about the future, and encourages me all the time to continue to enjoy life to the fullest.”
As a professor, Pearlmutter studied medical ethics. He even served on the MUSC’s ethics committee. But the experience of diagnosing and treating cancer gave him new insights.
Teach me that my students are a little smarter than me in some ways, because when you ask them a question, they’ll say, “Well, you have to be there.” And I think there are some things about cancer where you just have to be there. It was education, “he said.
Pearlmouth is grateful for the gift of ordinary days with his wife, four children and 11 grandchildren. For the past decade, their supportive friends have only helped by showing up – for coffee, a walk or a bridge game. Supported by family and friends, he was able to live a full life despite cancer, he said.
“Life is good,” he said. Waking up to work in the garden, check what is blooming and what fruits are ready to pick and watch the birds that are attracted to bird feeders, provides quiet joy. As well as the morning cup of coffee and the company of his family.
“Since I’ve been retired for the last three or four years, I’m just happy to have time and feel good, and I’m very grateful for that.”