Since scientists first discovered that human immune cells could be modified to become cancer-fighting agents, they've been trying to engineer a cell that's effective against solid tumors, which account for the vast majority of cancer cases.
In a key advance in meeting this "holy grail challenge" in the field of cancer cell therapy, a team of Yale scientists led by geneticist Sidi Chen has revealed how immune cells can be "boosted" to target and eradicate solid tumors.
The research was published in the journal Nature.
The field of cell therapy began to revolutionize cancer treatment several decades ago, when researchers pioneered the use of therapeutic cells. In this process, immune cells are removed from a patient, modified so that they can better fight cancer, and then reintroduced into the patient's body.
Two major streams of this therapy exist: CAR-NK cell therapy, which uses a patient's natural killer (NK) cells, and CAR-T cell therapy, which uses a patient's T cells. In both cases, scientists genetically modify the cells to express Chimeric Antigen Receptor (CAR), a synthetic receptor that helps immune cells recognize proteins on cancer cells.
But while CAR therapies have been successful in treating blood cancers, they're largely ineffective against solid tumors. Among other obstacles, these therapies struggle with poor infiltration into tumors and immune exhaustion.
In the new study, researchers discovered that adding a gene called OR7A10 to natural killer (CAR-NK) cells dramatically improved their ability to fight solid tumors. In multiple mouse model studies - targeting breast, colon, and ovarian cancers - the engineered cells showed far stronger tumor control than standard CAR-NK cells. In one breast cancer model, 100% of treated mice experienced complete tumor elimination.
