Bringing Immunotherapy Straight to the Source

Aparna Nathan in The Scientist:

In cancer immunotherapy, T cells are often the stars of the show. Many immune checkpoint blockade drugs keep cancer cells from evading T cells, and cellular immunotherapies arm T cells with chimeric antigen receptors (CAR). But Mattias Carlsten, a hematologist at the Karolinska Institute, switched to studying natural killer (NK) cells when he realized that they offered a unique opportunity to treat blood cancers like acute myeloid leukemia (AML).  Previous studies reported that NK cells are unique in that they target cancer cells without any prior training or specially engineered molecules like CAR.1 But NK cells did not efficiently penetrate the bone marrow, which as the source of AML cells, was a prime target for lasting treatment.

In a study published in the journal Leukemia, Carlsten’s team described a new way to engineer NK cells to head straight to the source for more potent anticancer immunity.2 By modifying molecules on the NK cells’ surfaces, they ensured that the immune cells homed to the bone marrow to hunt down cancerous cells. Carlsten thinks that this approach, which leverages molecules already found on NK cells, could make NK cell therapies a reality for blood cancers. “As a researcher, I like to capitalize on normal biology and take it from one context to another,” Carlsten said. In this study, the normal biology is two important cell surface molecules involved in NK cell function. First, Carlsten’s team focused on a receptor that binds the molecule E-selectin. In people with AML, bone marrow blood vessels increase E-selectin expression, which triggers signals that send the cancerous blood cells into a dormant state.3 The cells’ lack of activity hides them from chemotherapy, which targets dividing cells.   “If this is happening, why don’t we utilize this cue to home the NK cells better to this particular subsite of the microenvironment where the AML cells are?” Carlsten said.

More here.