Despite remarkable advances in cancer treatment over the past 25 years, cancer still claims the lives of more than half a million Americans each year. That’s half a million kids, parents, grandparents, friends, and spouses, whose lives were cut short by disease. For many patients, treatment arrived too late or did not work. For thousands, the unthinkable happened — they never had access to treatment at all.
Some cancers, like lymphoma, can be highly treatable. Yet, among patients who initially respond to first-line therapy, nearly one in three will relapse — and once the disease returns, it becomes more difficult to treat. For newly diagnosed patients with large B-cell lymphoma (LBCL), there’s new hope. The ALPHA3 trial sponsored by Allogene Therapeutics is testing an “off-the-shelf” form of Chimeric Antigen Receptor T-cell, or CAR T therapy — a groundbreaking immunotherapy designed to be available without the wait required for individualized treatments. The trial is designed to detect disease and treat patients at greater risk before relapse makes the disease harder to cure. We spoke with Yuliya Linhares, MD, a medical oncologist specializing in the treatment of lymphoma about what sets CAR T therapy apart from traditional cancer treatment and what this breakthrough could mean for the future of cancer care.
Blunt Force vs. Precision Power
Chemotherapy has long been a cornerstone of cancer treatment, but it acts like a broad, indiscriminate weapon — powerful, yet damaging to both cancerous and healthy cells. “Most chemotherapy drugs damage DNA in all cells they encounter, affecting cancer and normal cells alike,” explains Dr. Linhares. By contrast, CAR T therapy takes a more precise and innovative approach, using living cells as medicine. As Dr. Linhares describes, these engineered cells are “live organisms made better at what they’re already good at: killing cancer cells.”
To understand how CAR T works, you’ve got to understand your immune system — specifically, the role of T cells. “These are beautiful cells programmed to keep us healthy by killing off invaders, like bacteria or viruses,” explains Dr. Linhares. In theory, T cells should also be able to attack cancer. But cancer cells often slip past detection because T cells mistake them as normal parts of the body. As a result, the cancer is able to grow and multiply unchecked, quietly spreading while evading the body’s usual defenses.
CAR T therapy was designed to fix that blind spot, training our own T cells to better recognize and destroy cancer cells. The process begins by collecting a patient’s own T cells from their blood and genetically modifying them in a lab to become what Dr. Linhares describes as a kind of personalized bio-weapon: “Scientists modify these T cells to recognize cancer cells as dangerous, triggering a powerful killing response.” Once infused back into the patient, these supercharged T cells don’t just attack cancer cells more effectively — they multiply whenever they encounter their target. This creates a growing army of cancer-killing cells that zero in on unique markers, or antigens, found only on cancer cells, while leaving healthy cells alone.
But while this highly personalized approach can be lifesaving, it also comes with major logistical hurdles. Manufacturing CAR T from each individual patient’s cells — also referred to as autologous — is complex, time-consuming, and limited to highly specialized treatment centers, often far from where patients live. Today only about 20 percent of eligible patients are able to access CAR T, despite there being several FDA-approved products.
That’s why researchers are developing “off-the-shelf” CAR T therapies — ready-made versions built from healthy donor cells — that could deliver the same cancer-fighting power without the delays or geographic limitations of the current process.
“Off-the-shelf” or allogeneic CAR T uses healthy donor cells that are already collected, modified, and ready to go. Think of it almost like a blood bank: Using donor cells allows hospitals to have the treatment available and in-hand without requiring the patient to travel to a major academic medical center. “With autologous therapy,” explains Dr. Linhares, “we’re building a personalized weapon from scratch each time. With allogeneic, it’s like having a shelf of ready-made, high-quality tools we can grab the moment a patient needs them.”
And the promise doesn’t stop there: Scientists are now exploring ways to move CAR T into earlier stages of treatment, when patients’ immune systems remain stronger, creating the potential for even greater benefit.
A Shift from Last Resort to Preemptive Strike
At this point, CAR T is only approved for patients whose cancer has either recurred or who have not responded to other treatment. That means CAR T is typically offered after a patient has already tried and failed one or more rounds of chemotherapy: “Like any new cancer therapy, it’s first tested in people who don’t have other options,” says Dr. Linhares. “Many of these patients were very sick, and CAR T offered new hope — in fact, it outperformed standard chemotherapy in people who had little chance left for a cure.”
As more data emerges, CAR T is being considered earlier in the treatment process for some cancers, and clinical trials are testing whether it could be used as a first-line treatment for aggressive lymphomas. But CAR T should only be used on patients who truly need it: those at highest risk of relapse.
“Right now, about 60 percent of patients go into complete remission,” she explains, meaning their cancer no longer shows up on scans after initial treatment. “But even those who achieve remission can subsequently relapse — and historically we’ve had no way of knowing who those patients would be.”
Even if doctors had been able to identify those at higher risk, there is currently no effective way to intervene and prevent relapse. Traditionally, doctors have used the “watchful waiting” technique, monitoring patients with regular scans and physical exams. While watchful waiting can help patients avoid unnecessary treatment, it may allow cancer to progress and brings the stress of living with uncertainty. “We’re basically sitting there and waiting for the relapse,” says Dr. Linhares.
A new clinical trial is pairing “off-the-shelf” CAR T with a quick and easy blood test that detects faint traces of residual cancer and identifies patients most at risk of relapse right after initial therapy.
“It’s like a cancer ‘signature,” says Dr. Linhares, “and this test can detect it even when nothing shows up on imaging.” A positive result means there’s about an 85 percent chance of relapse within three years. When the result is negative, the chance of relapse is less than 15 percent.” The hope is that this blood test — known as minimal residual disease or MRD — can help doctors identify patients at greatest risk of relapse early. But it’s the use of CAR T therapy in this high-risk group that has the potential to stop relapse before it happens. In other words, MRD pinpoints the threat, and CAR T may neutralize it. For patients, families, and the healthcare system, the benefits of earlier, more targeted intervention could be profound. As Dr. Linhares puts it: “It’s like sweeping the floor clean before the dust has a chance to settle — treating the disease at a microscopic level before it becomes symptomatic or visible.”
If successful, this approach could transform cancer care — shifting away from watching and waiting to moving early, and with precision. Instead of simply responding to relapse, it could open the door to preventing relapse in the first place. “This is the future,” Dr. Linhares says. “When you’re able to treat a relapse at a very early stage, you can potentially reduce side effects and be more effective. It’s a win-win — but we need trials like ALPHA3 to prove it.”
