mRNA vaccines came of age during the COVID-19 pandemic; now scientists are using them against cancerCredit: Kateryna Kon/Shutterstock
Can messenger RNA (mRNA) train the immune system to attack cancers that resist conventional treatments? To find out, researchers at Atlantic Health System are conducting a clinical trial, alongside other centres, to evaluate the efficacy of an experimental mRNA vaccine for patients with late-stage melanoma, the most lethal form of skin cancer.
“This trial really resonates with patients,” says oncologist, Eric Whitman, medical director of Atlantic Health’s oncology service line, who is leading the study locally at Morristown Medical Center (MMC) in New Jersey. “They’ve heard how effective mRNA COVID-19 vaccines are; using a similar technology to help their body recognize and destroy melanoma makes sense to them.”
There is a dearth of effective treatments for melanoma, which kills about 8,000 people in the United States annually. Standard therapies fail to halt cancer progression in about 50% of patients, leaving them with no FDA-approved options.
Called BNT111, the candidate vaccine targets four cancer-specific proteins, or antigens, that are prevalent in melanoma cells. Manufactured by BioNTech, BNT111 has shown1 it can elicit a strong immune response to the target antigens. “Of all the cancers we treat, melanoma seems to have the strongest tie to the immune system, so we’re very hopeful that patients will benefit from this vaccine,” says Whitman.
The vaccine study is one of about 100 groundbreaking clinical trials underway at Atlantic Health, one of New Jersey’s largest non-profit health-care networks. Its physician-scientists are exploring innovative approaches to complex cancers, including lymphoma, leukaemia, melanoma, pancreatic cancer and other solid tumours, and are proud to deliver these efforts in a community hospital setting.
Fast-track oncology breakthroughs
Over the past four years, Atlantic Health has dramatically expanded its portfolio of clinical trials through collaborations with government and industry groups. In 2019, Atlantic Health Cancer Consortium — comprising leading medical centres across the state — was designated as New Jersey’s first and only National Cancer Institute (NCI) Community Oncology Research Program (NCORP) site, giving it access to a vast array of NCI-supported cancer studies, some of which are exclusively available at NCORP sites.
That same year, Atlantic Health also partnered with Translational Genomics Research Institute (TGen) to create the Breakthrough Oncology Accelerator, a programme focused on phase I trials: first-in-human studies of new drugs and technologies for patients whose cancers have progressed on all previous therapies. The goal is to fast-track the development and testing of affordable and potentially lifesaving new treatments for cancers that are currently difficult or impossible to manage.
“Through our close collaboration with TGen, we have access to a constant pipeline of very exciting new anti-tumour agents,” says Angela Alistar, an oncologist and medical director of the Breakthrough Treatment Center at MMC, a new, state-of-the-art facility with a dedicated phase I infusion unit. “We have the research team and infrastructure to support studies ranging from intra-tumoral drug delivery to cancer vaccines and the newest cell-based therapies.”
Alistar is currently co-leading a phase I multicentre trial of an oral drug for patients with advanced solid-tumour cancers, such as those affecting the colon, kidneys and other organs. “Most clinical trials target cancer cells, but the compound we are testing manipulates the tumour micro-environment in which they live,” she explains. The goal is to change the microenvironment from one that helps cancer cells evade the immune system to one that suppresses and contains them.
Cell therapies for blood cancer
Atlantic Health’s leukaemia and lymphoma research programme has been particularly successful, with patient numbers doubling over the past four years, according to Mohamad Cherry, Atlantic Health’s medical director of haematology/oncology.
“Blood cancers are highly complex to treat, so many community oncologists refer patients to large academic medical centres,” says Cherry. These centres will often administer advanced treatments, such as CAR-T (chimeric antigen receptor T cell therapy) on an in-patient basis. “That’s expensive and inconvenient, since patients prefer to be treated locally,” he adds. To see if CAR-T can be safely administered in community settings, Cherry and other investigators launched the Outreach Study.
Outreach compared inpatient and outpatient outcomes in patients with aggressive non-Hodgkin’s lymphoma who were treated with a CAR-T product called Liso-cel. Early findings2 revealed that the treatment may actually be more effective in outpatients, with 68% of those studied exhibiting a complete response to the therapy, versus 50% of the inpatients.
CAR-T involves removing T cells from the patient and genetically engineering them to contain receptors specific to cancer cells. The CAR-T cells are then infused into the patient, which is why they are called a ‘living drug’, explains Cherry. “The beauty of this treatment is that these immune cells can live in the body for months and keep chasing the cancer down.”
Celebrating medical miracles
Atlantic Health’s success in fast-tracking trials of the newest therapies is attracting patients from other states, even those with their own renowned cancer centres, reports Charles Farber, Atlantic Health’s medical director of oncology research. “A few years ago, I got an urgent call from a man in his 70s, asking about a trial we were conducting of a new drug for Waldenstrom Macroglobulinemia (WM),” a rare form of lymphoma affecting about three in one million Americans annually. “He’d been told that the centre, where he was being treated, would offer that trial in six months — but he was so sick that he wasn’t likely to live that long.”
When the man arrived at MMC to enrol in the WM study, having travelled hundreds of miles from his home, he was in a wheelchair and gasping for breath. What’s more, he’d already been in two previous clinical trials, neither of which had halted the disease’s relentless progression, continues Farber. “Within a few weeks of entering the trial, he had a magnificent response to the drug we were testing, which was FDA approved 18 months later.”
The patient went into complete remission and is now leading a healthy active life that includes his favourite sports. “He sent me photos of his new mountain bike,” adds Farber. “It was wonderful to see him restored to doing the things he loved.”