i3S develops “highly effective” therapy against aggressive tumors

Researchers at the Institute for Research and Innovation in Health at the University of Porto (i3S) have developed a new CAR T-cell therapy that shows “highly effective” results against solid tumors such as stomach, pancreatic, and ovarian cancer. Published in the journal Cell Reports Medicine, the study marks a significant breakthrough in immunotherapy, opening new possibilities for patients with cancers that currently have very limited treatment options.

Rafaela Abrantes and Celso A. Reis focused on a glycan that is absent in healthy tissues but abundantly expressed in many epithelial tumors, such as gastric, pancreatic, and colorectal tumors.

Targeting a unique tumor marker
The team, led by Celso A. Reis, head of the Glycobiology in Cancer group at i3S and professor at ICBAS, focused on a glycan known as Sialyl-Tn (STn). This sugar structure is absent from healthy tissues but appears abundantly in many epithelial cancers, including gastric, pancreatic, and colorectal tumors.

“Selecting a highly specific tumor target is crucial for the success of T-cell therapies,” explains Rafaela Abrantes, first author of the paper and researcher at i3S. “That’s why we chose STn—it’s a marker that is virtually invisible in healthy tissues but highly present in several aggressive cancers.”

From antibody to engineered immune cells

To target this marker, the researchers created a new monoclonal antibody, AM52.1, designed to recognize STn. Using it, they engineered Chimeric Antigen Receptors (CARs) and introduced them into T cells from the patient’s own immune system. The resulting CAR T cells were able to identify and selectively eliminate tumor cells carrying STn.

“In our preclinical tests, these CAR T cells proved to be highly effective, robustly activating, producing inflammatory cytokines, and efficiently destroying tumor cells,” says Celso A. Reis.
Strong results in preclinical models

The therapy, named AM52.1CAR T, was tested across several preclinical models—from organoids to animal models with patient-derived tumors. Results showed strong tumor elimination even in cancers with low levels of STn or with features that typically make solid tumors resistant to cell therapies.

Equally important, the treatment showed no toxicity or adverse effects in preclinical studies, a critical step toward ensuring patient safety.
A promising path toward clinical trials

This work, carried out in collaboration with the Cellular Therapy Unit at Oslo University Hospital, highlights the strong translational potential of AM52.1CAR T for future clinical trials.
“With this study, i3S positions itself at the forefront of targeted therapies and immunotherapy for solid tumors,” emphasizes Celso A. Reis. “Our results propose a promising strategy that, in the near future, may be applied to patients facing cancers that remain very difficult to treat.”