A research team led by Sebastian Kobold at LMU University Hospital has developed a new approach to enhance the effectiveness of CAR T cell therapy against solid tumors. The study, conducted in collaboration with Jan Böttcher from the University of Tübingen, was published in Nature Biomedical Engineering.
Previous work by Kobold's group showed that prostaglandin E2 (PGE2), a metabolite found near tumors, can suppress the activity of T cells—immune cells responsible for attacking cancer. This suppression is one reason why CAR T cell therapies have not been successful in treating solid tumors such as bowel or pancreatic cancer.
To address this challenge, the researchers modified CAR T cells so that PGE2 can no longer bind to them. This genetic alteration prevents PGE2 from exerting its immunosuppressive effect on the engineered immune cells. In experimental models involving breast and pancreatic cancer, these modified CAR T cells were able to control tumor growth. They also showed high effectiveness when tested on tumor samples from human patients with pancreatic or bowel cancer and neuroendocrine tumors.
CAR-T therapy involves extracting a patient's own T cells and genetically engineering them to recognize specific proteins on cancer cells. When reintroduced into the body, these modified cells target and kill cancerous cells. While this approach has been effective for certain blood cancers like leukemia and lymphoma, it has faced obstacles with solid tumors due to their ability to evade immune responses.
Janina Dörr, lead author of the study, stated: "Soon it will be possible to test our approach in clinical studies." She noted that initial trials will focus on patients with lymphomas rather than those with solid tumors. According to Sebastian Kobold: "According to our findings, there is a good chance that therapy with silenced PGE2 will be considerably more successful." If results are positive and funding becomes available, future studies may include patients with solid tumors.
