When the FDA announced in 2017 that it was approving an immunotherapy treatment for children with certain relapsed blood cancers, doctors and patients were pretty excited. That treatment, tisagenlecleucel (brand name Kymriah), involves engineering the patient's own immune cells to make biological chimeras, called CAR-T cells, that recognize and attack cancer.
But on the heels of that excitement came a question: When would this approach be available for other pediatric cancers? Children with solid tumors — including tumors of the brain, nerve cells, bones and muscle — need better treatments, especially in cases where the tumors spread around the body or the patient relapses after receiving traditional chemotherapy and radiation. However, those tumors don't carry the same surface markers that the existing therapy goes after.
Now, with findings reported today in Clinical Cancer Research, Stanford scientists have moved a big step closer to using CAR-T cells for solid tumors in children. They've shown that a protein called B7-H3 is abundant on many kinds of pediatric cancer cells — including certain tumors that occur in the brain, nerve cells, bone and muscle — and that B7-H3 makes a good immunotherapy target. They have successfully engineered CAR-T cells to go after B7-H3 and tested them in mice implanted with human tumors.
In mice with osteosarcoma or Ewing sarcoma — both bone tumors — B7-H3 CAR-T cells eradicated the tumors. The treated mice lived significantly longer than animals that received a control treatment.
'The tumor just goes away,' Majzner said. 'It’s very consistent. It happened in all the mice, and that’s exciting.'
A group of mice with osteosarcoma had their initial tumors surgically removed and then received B7-H3 CAR-T cells to test whether the cells could treat cancer cells that had spread to the lungs. Again, the CAR-T cells worked; the treated mice lived significantly longer than those in a control group.
The next research step is human clinical trials. The B7-H3 protein is not found on any healthy tissues in the central nervous system, so Majzner and his colleagues plan to begin the human studies in adults with brain tumors.
One exciting aspect of the work is the fact that the same target is abundant on so many different cancers, Majzner told me. That means that if the clinical trials succeed, a commercially viable treatment is more likely, and, ultimately, more patients could be helped.
Photo by Steve Fisch