Scientists created a new cancer immunotherapy approach that uses a new type of CAR T cells to stimulate an immune response against cells that are missing one gene copy. They reported their findings in Proceedings of the National Academy of Sciences.
Termed NASCAR (neoplasm-targeting allele-sensing CAR) T cells, the treatment binds to and kills cells with loss of heterozygosity (LOH), turning the missing gene copy into an immune cell-activating signal. The approach relies on a NOT gate or an if/then mechanism to turn the T cell on or off. If both gene copies are present—A and B—the inhibitory molecule is functioning correctly and the NASCAR T cells remain dormant. If one gene copy is present and the other is missing—A and not B—then the NASCAR T cells are activated and kill the cancer cell.
The researchers successfully tested the treatment in three independent cell lines and in mouse models, but future studies are needed before the therapy may reach clinical practice. They have additional studies planned to expand it to other genes that undergo LOH and to more precisely regulate CARs.
“This study provides proof-of-principle that this approach can be used to selectively kill cancer cells,” the researchers said, with the goal of extending immunotherapy’s benefits to many more patients and types of cancer.