NEW YORK, Nov. 3, 2025 /PRNewswire/ — The DeGregorio Family Foundation with support from the Torrey Coast Foundation has awarded a $750,000 Michael F. Price Memorial Grant to Eric Smith, MD, PhD, and Andrew Aguirre, MD, PhD, both of Dana-Farber Cancer Institute, and Sam Klempner, MD, Massachusetts General Hospital. The grant is for clinical translation of a novel dual-targeted CAR T cell therapy for advanced gastroesophageal cancer.

Traditional chemotherapies have largely failed to control advanced gastric and esophageal cancers. One promising alternative is Chimeric Antigen Receptor (CAR) T cell therapy, which reprograms a patient’s own immune cells to seek and destroy cancer. CAR T cells have transformed some blood cancers. This project adapts next–generation CAR T technology specifically for gastric and esophageal adenocarcinomas (GEA), using a dual–target design and rapid manufacturing to treat more patients and aim for more frequent, deeper and more durable responses.

Early CAR T trials in GEA targeting a protein called CLDN18.2 have shown that tumors can shrink – an encouraging sign in a solid tumor. But responses often don’t last. A major reason is that CLDN18.2 isn’t present at high levels in every patient’s tumor, and even within a single tumor it can be patchy. Cancer cells are also “shape–shifters”: under treatment pressure they can change their outer “coat” and turn markers like CLDN18.2 down or off, helping them hide from single–target therapies. This patchwork and shape–shifting behavior (tumor heterogeneity and plasticity) makes it harder to achieve deep, durable remissions.

Building on our prior work, including analysis of more than 80 patient tumor samples, we designed dual–CAR T cells that act when they detect either of two tumor markers – an “OR–gated” approach that covers patchy tumors and makes it harder for cancer to escape. We optimized fully human components to reduce the risk of rejection and tuned their affinity to latch onto tumors while minimizing the chance of harming healthy tissues. In laboratory and animal models, these dual–CARs eliminated fast–growing, high–burden GEA tumors. In parallel, our rapid manufacturing process returns fitter CAR T cells to patients more quickly and has been associated with stronger expansion and persistence – features linked to more durable responses.

We have selected a lead dual–CAR candidate (with a backup) and are entering the final preclinical stage required to open a first–in–human Phase I trial for patients with advanced GEA. The trial will determine safety and the recommended dose, while also studying who benefits and why, with the goal of expanding eligibility beyond CLDN18.2–high patients and delivering more frequent, deeper and longer–lasting responses.

Co–PIs Dr. Smith, Dr. Aguirre and Dr. Klempner all agree: “DeGregorio Family Foundation funding is uniquely enabling at this stage. This is high–risk, high–reward translational work – moving a novel cellular therapy from the lab into first–in–human testing – and in today’s funding climate, other funding mechanisms are not designed to support this critical step. Without the Foundation’s commitment, patients with gastric and esophageal cancers would not be able to access this innovative treatment.”

“We are honored to support this exciting next step in the research towards dramatically improving immunotherapy for gastroesophageal cancer patients,” concluded Lynn DeGregorio, President and Founder of the DeGregorio Family Foundation, the only public foundation solely focused on funding research grants for both gastric and esophageal cancers.

In 2020, gastric and esophageal cancers combined killed over 1.3 million people worldwide. Patients continue to face poor prognoses following gastric and esophageal cancer diagnoses due to their chemo-resistant behavior and ability to metastasize.

The DeGregorio Family Foundation, founded in 2006 after a 10th member of the DeGregorio family died of stomach cancer, has raised more than $13 million to fund innovative research to cure gastric and esophageal cancers. It is the only public foundation focused on funding research grants for both of these cancers.

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