Scientists at St. Jude Children’s Research Hospital have discovered that removing the gene for Regnase-1 from engineered immune cells makes them more effective at treating relapsed osteosarcoma. There is a great clinical need for new therapies for childhood osteosarcoma, for which there are very few effective treatments for relapsed disease. The approach improved the cells’ ability to control osteosarcoma growth and prevent metastasis to the lungs in preclinical models. The findings support the development of an early-phase clinical trial and were published today in Cell Reports Medicine.
Chimeric antigen receptor (CAR) T-cell therapy reprograms a patient’s own immune cells to recognize and attack cancer. The treatment has shown success in some relapsed childhood leukemias, but it has not worked as well against solid tumors, including osteosarcoma. One major reason is that the tumor microenvironment, the local area around the tumor, can suppress anticancer immune activity and cause CAR T cells to become less functional.
To overcome these barriers, the St. Jude group removed the gene for Regnase-1 (which normally acts as a “brake” on immune function) from CAR T cells, then tested the modified cells in mouse models of osteosarcoma.
