Optimized CAR Shows Promise Against Solid Tumors

Researchers at the Montefiore Einstein Comprehensive Cancer Center (MECCC) have shown that a breakthrough therapy for treating blood cancers can be adapted to treat solid tumors—an advance that could transform cancer treatment

While CAR-T cell therapy has revolutionized the treatment of blood cancers like leukemia and lymphoma, it has not been as effective against solid tumors. Xingxing Zang, senior author of the study published in Science Advances, and his team found that by modifying standard CAR-T cell therapy, they could significantly boost its effectiveness against solid tumors, including often-fatal pancreatic cancer and glioblastomas.

The team created five CAR-T therapies and tested them on mice implanted with several types of solid human tumors. One therapy, which used two novel components, proved superior in safely and effectively shrinking glioblastoma, pancreatic, and lung cancer tumors.

The most effective therapy, called the TMIGD2 Optimized Potent/Persistent (TOP) CAR, incorporated a novel antibody that binds to the B7-H3 antigen, widely expressed on solid tumors and their blood vessels. Additionally, it utilized a protein called TMIGD2, discovered by Dr. Zang, as a costimulatory protein to activate T cells and enable them to overcome the hostile microenvironment of solid tumors.

The TOP CAR-T therapy proved best at keeping mice with pancreatic, lung, and glioblastoma tumors alive, outperforming other CAR-T therapies in key effectiveness and safety parameters. Dr. Zang plans to further develop TOP CAR into an off-the-shelf platform that can target multiple tumor antigens and be tailored for treating various types of solid tumors.