A compound that sparks an immune system attack on cancer while also lowering tumor cells’ defenses against such an attack is showing promise in its first clinical trial in patients with advanced or metastatic cancers. One of those with the best result is a former U.S. Marine and Afghanistan war veteran, Josh Mahoney.
Mahoney, of Quincy, Mass., enrolled in the trial at Dana-Farber in 2020 after experiencing a recurrence of oligodendroglioma, a rare form of brain cancer involving cells that produce a protective substance for nerve cells. The agent being tested, MCLA-145, is a bispecific antibody — a compound that binds to two different proteins, one on immune system T cells and one on tumor cells. This dual connection prompts T cells to multiply and mobilize against cancer and simultaneously causes tumor cells to let down their guard against a T cell attack.
As part of the trial, Mahoney receives an infusion of MCLA-145 every two weeks and has an MRI scan every month to check for cancer. Two years into the trial, he has no sign of his former tumor, says his oncologist, David Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber.
Clues to a diagnosis
Mahoney was first diagnosed with oligodendroglioma in 2009, but the clues that something might be wrong began a few months earlier. Back from his first overseas deployment with a Marine Expeditionary Unit, he started experiencing symptoms that, in someone less strong-willed, would have prompted a visit to a doctor.
“Half of my face would go numb from time to time; I’d have trouble swallowing and had tingling in my hand that went from finger to finger,” says Mahoney, a married father of a two-year-old daughter. “As a psychology major in college, I kind of knew the issues I was having were neurological, but I ignored them.” He downplayed them, to himself and others, to remain eligible for deployment to Afghanistan.
He served in Afghanistan for seven months in early 2009. An infantry platoon commander, he went on patrols, served as watch officer while other units were on patrol, and relayed intelligence. “We had a great company commander who’d established a good rapport with the local village,” Mahoney says. “They treated us well, we treated them well — we weren’t engaged in a lot of fighting.”
The neurological problems continued during his time in Afghanistan. Toward the end of his deployment, a doctor conducted a neurological exam, minus an MRI scan, and told him he was moving a little slowly on one side of his body. He recommended a more extensive exam once Mahoney got back to Camp Pendleton, in California, where he was based.
It was an appointment he never had a chance to schedule. Shortly after returning to Camp Pendleton, he was on leave in Las Vegas with friends when he had a seizure in his hotel room and passed out on his bed.
He was rushed to the hospital, where a scan revealed a tumor. A biopsy showed it to be oligodendroglioma. “At one point, they told me it was the size of a grapefruit,” Mahoney recalls. A surgeon in Las Vegas removed the bulk of the tumor but, lacking access to intraoperative MRI technology — which provides surgeons with live images of the brain — had to leave some behind for later removal.
From Vegas to Boston
“My family came out to Las Vegas, and my mother researched the best place to get the rest of my treatment,” Mahoney recounts. “We decided on Dana-Farber.”
In Boston, he underwent a second operation followed by a year of chemotherapy and radiation therapy. He received a medical discharge from the Marines and by 2011 his life was “somewhat back to normal,” he says, with a new job in research administration for the Department of Veterans Affairs.
Every few months at first and then once a year, he would come to Dana-Farber for a check-up and MRI scan. In 2019, a scan showed a small growth, which turned out to be a recurrence of his cancer in a more aggressive form. He underwent an operation to remove the regrowth of the tumor and enrolled in the trial of MCLA-145, which is testing the drug in patients with a variety of different tumor types. He’s done well on the trial: the only major side effect was an inflammation of the liver, which subsided when the dose was adjusted.
“This trial is part of an effort to improve on the first generation of cancer immunotherapies, which weren’t very effective for people with brain cancer or certain other cancers,” Reardon remarks. “We’re working to build on the insights we gained in earlier trials. We’ve very encouraged by the results Josh has had so far.”
Mahoney recounted his experience with oligodendroglioma at this year’s WEEI NESN Jimmy Fund Radio-Telethon. To listen, click here.