A Second Chance at a Cure: Rescuing a Revolution in Cancer Therapy

NATICK, Mass. & LONDON – December 08, 2025

It is one of modern medicine’s most stunning achievements: reprogramming a patient’s own immune cells into a “living drug” that hunts and destroys cancer. CAR T-cell therapy has been nothing short of revolutionary for patients with aggressive B-cell malignancies, offering durable remissions to those who had exhausted all other options. But for every story of a miraculous cure, there is a quieter, more devastating narrative. For up to 60 percent of patients, this last-resort therapy ultimately fails. The cancer returns, often more cunning than before, leaving patients and their families with dwindling hope and few, if any, paths forward.

This is the critical human challenge at the heart of immuno-oncology's next frontier. It’s not just about creating powerful new therapies, but about ensuring they last. Now, a new collaboration between Aleta Biotherapeutics and Cancer Research UK is tackling this problem head-on. Promising early data from a clinical trial for a biologic named ALETA-001 suggests a potential breakthrough: a way to rescue failing CAR T-cell treatments and give patients a second chance at a cure.

When a Living Drug Loses Its Way

To understand the significance of ALETA-001, one must first appreciate the biological chess match that leads to CAR T-cell failure. CAR T-cell therapy involves extracting a patient's T-cells - the soldiers of the immune system - and genetically engineering them to recognize a specific protein, or antigen, on the surface of cancer cells. For B-cell cancers, the most common target is an antigen called CD19.

When these supercharged cells are reinfused into the patient, they multiply and launch a precise, powerful attack on any cell bearing the CD19 marker. The results can be dramatic. Yet, cancer is a master of evolution. Under the intense pressure of a CAR T-cell assault, tumor cells can adapt to survive. The most common escape strategy is known as antigen loss. The cancer cells effectively change their identity, shedding the CD19 marker from their surface. They become invisible to the very 'living drug' designed to kill them, allowing the disease to relapse.

For a patient who has endured the rigors of CAR T-cell therapy, this outcome is crushing. The engineered T-cells may still be circulating in their body, ready to fight, but they are patrolling for a target that no longer exists. This is where the prognosis turns grim, with median survival often measured in months. The challenge, then, is not the potency of the T-cells, but the identity of the tumor.

Repainting the Target for a Second Attack

This is the problem Aleta Biotherapeutics was built to solve. Instead of creating an entirely new CAR T-cell therapy, ALETA-001 is designed as an elegant, 'off-the-shelf' partner to the original treatment. It's a CAR T-cell engager (CTE) that acts as a molecular bridge, effectively repainting the cancer cells so the existing CAR T-cells can find them again.

The biologic has a unique dual-action mechanism. It's designed to bind to a different, more stable antigen on the lymphoma cell surface called CD20. Once attached, the other end of ALETA-001 displays a copy of the very CD19 protein the cancer cell may have shed. In essence, it forces the tumor to wear its old target identity again, whether it wants to or not. This restores the 'lost' CD19 expression and dramatically increases the overall density of the target, making the cancer cells highly visible and vulnerable to the CD19-directed CAR T-cells already circulating in the patient.

Early results from the phase I/II clinical trial, sponsored and conducted by Cancer Research UK’s Centre for Drug Development, are validating this innovative approach. In patients who had relapsed or failed to achieve remission after CAR T-cell therapy, ALETA-001 demonstrated a highly tolerable safety profile. More importantly, it showed clear signs of working as designed. Robust expansion of the previously administered CAR T-cells was observed in a majority of patients even at low doses, proving the biologic was successfully reigniting the immune attack. Most encouragingly, a proportion of these high-risk patients achieved durable complete metabolic remissions - a clinical sign that the cancer has been cleared.

As Marco Ruella, a scientific advisor to Aleta and a leading expert at the University of Pennsylvania, noted, “Having agents that can enhance or even rescue CAR T-cell anti-tumor activity is highly desirable. These promising preliminary clinical results initially suggest that ALETA-001 can revitalize CAR T-cells that have struggled to clear the tumor.”

Building a Resilient System of Hope

The development of ALETA-001 is a story not just of scientific ingenuity, but of strategic collaboration and a systems-level approach to healthcare innovation. The partnership between a nimble U.S. biotech and the formidable research and development engine of Cancer Research UK highlights a global commitment to solving medicine's toughest challenges.

This commitment is further underscored by the UK's Innovative Licensing and Access Pathway (ILAP). ALETA-001 received an 'Innovation Passport' under this program, a designation reserved for medicines addressing life-threatening conditions with a significant unmet need. The ILAP is designed to accelerate development and patient access by creating a collaborative roadmap between developers and regulatory bodies. It’s a framework built on the understanding that for patients in dire situations, time is the most precious commodity.

“The majority of B-cell lymphoma patients relapse early after CD19-targeted CAR T-cell therapy,” said Dr. Sridhar Chaganti, the trial’s Chief Investigator. “For these patients, time is critical and outcomes with further treatments are poor. ALETA-001 is a promising, off-the-shelf therapeutic that... offer(s) the potential for a cure.”

This approach signals a mature new phase in personalized medicine. It acknowledges that even our most advanced technologies can fail and focuses on building in resilience. The trial is now exploring administering ALETA-001 proactively, shortly after the initial CAR T-cell infusion, to prevent relapse before it even begins.

“This is an exciting milestone,” said Paul Rennert, President and Chief Scientific Officer at Aleta Biotherapeutics. “ALETA-001 is now being provided to patients shortly after they receive a CD19 CAR T-cell therapy, giving these patients the opportunity for a robust and durable response.” It’s a shift from a reactive rescue mission to a proactive strategy of reinforcement, ensuring the revolutionary power of CAR T-cell therapy is not a fleeting victory, but a lasting one.