When genetically modified with a chimeric antigen receptor (CAR), natural killer T (NKT) cells eliminated 50% of metastases in a patient with heavily pretreated, relapsed or refractory metastatic neuroblastoma, according to interim findings from an ongoing study that were published in Nature Medicine.
Initial studies of CAR therapies—and today’s approved indications—all used immune T cells, but the body has other types of T cells and researchers have been studying whether they may be more effective for cancer treatments. The current study’s authors’ preclinical studies showed that NKT cells may enhance CAR immunotherapy because they have a spectrum of antitumor activities.
First, the cells are able migrate to tumor sites to kill tumor-associated macrophages; then, NKT cell activation indirectly promotes an antitumor response mediated by two other types of immune cells, NK and T cells.
The researchers’ phase I study is small, with only three patients, and it’s ongoing. But so far the results demonstrated that the patients’ own CAR-enhanced NKT cells expanded upon infusion and localized to the tumors, with one of the patients experiencing regression of bone lesions. Additionally, none of the patients developed dose-limiting toxicities.
“Our study shows that it is possible to employ immune cells with natural antitumor capabilities and enhance their tumor fighting power with designer synthetic receptors, opening the possibility of applying this strategy to combat hard-to-treat solid tumors,” the researchers said.