Developing a new CAR-T Therapy

This cell therapy targets a specific sugar molecule called sialyl-Tn (STn), which is found on many solid tumors but is very rare in healthy tissue.

The project, a collaboration between Oslo University Hospital (OUS) and the University of Porto, represents a great achievement. In early lab tests, these new "AM52.1CAR" T cells successfully killed cancer cells while leaving healthy tissue unharmed with no observed side effects.

Incubator baby

“It’s our incubator baby,” Sébastien Wälchli, Principal Investigator from the Translational Research Unit at the Department of Cellular Therapy, OUS, stated.

He explained that all the experiments run by the Norwegian team were conducted almost entirely at the Oslo Cancer Cluster Incubator, except for the antibody isolation, which our colleagues performed at the Department of Medical Biochemistry, OUS.

This breakthrough brings immunotherapy a step closer to becoming a safer and more effective option for a wider range of patients. The results were recently published in the journal Cell Reports Medicine.

Read the article in Cell Reports Medicine.

A flag on cancer cells

CAR-T cell therapy works by taking a patient's own immune cells to seek and destroy cancer cells. While this approach has shown great success in blood cancers, progress with solid tumors has been limited in part by the difficulty of finding a cancer-specific target.

The scientists’ solution was to target STn, a sugar molecule that acts as a “flag” on the surface of many cancers but is rarely found in healthy tissue. They first developed AM52.1, a highly specific antibody that binds only to STn. Using this antibody, they created a new CAR-T cell capable of binding only to this sugar marker.

“AM52.1CAR T cells pleasantly exceeded all our expectations with their remarkable efficiency,” said Christopher Forcados, postdoc at the Translational Research Unit, OUS, and co-first author of the article in Cell Reports Medicine.

CAR T cells train the body's own immune cells to find and destroy only the cancer cells with the STn flag.

From lab to clinic

In preclinical tests, the new therapy successfully killed cancer cells in lab dishes and in mouse models, while leaving healthy tissue unharmed. The therapy is expected not to be toxic in humans.

Despite the encouraging data, the hardest part still lies ahead: moving from laboratory success to clinical trials.

“We need clinicians who are motivated to run a clinical trial; otherwise, what we’re doing preclinically becomes useless,” said Wälchli, underlining that they have excellent scientists in the team, ready to provide full support to a clinical research team, taking this innovative therapy all the way to the patients, and ideally to benefit Norwegian patients first.

Read more

The article in the journal Cell Reports Medicine

Have any questions about the research described? Contact the research team at OUS