HSC-iNKT Cell Therapy Shows Promise in Preclinical Study

UCLA researchers have shown they can harness the power of invariant natural killer T cells to attack tumor cells and treat cancer. In a paper published earlier this month in Cell Stem Cell, they describe a new method that effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models.

"What's really exciting is that we can give this treatment just once and it increases the number of iNKT cells to levels that can fight cancer for the lifetime of the animal," said Lili Yang, the study's senior author.

Scientists have hypothesized that iNKT cells could be a useful weapon against cancer because it has been shown that they are capable of targeting many types of cancer at once. But most people have very low quantities of iNKT cells; less than 0.1% of blood cells are iNKT cells in most cases. Still, Yang and her colleagues knew that previous clinical studies have shown that cancer patients with naturally higher levels of iNKT cells generally live longer than those with lower levels of cells.

The researchers' goal was to create a therapy that would permanently boost the body's ability to naturally produce more iNKT cells. They started with hematopoietic stem cells, which they genetically engineered so that they were programmed to develop into iNKT cells.

They tested the resulting cells, called hematopoietic stem cell-engineered invariant natural killer T cells, or HSC-iNKT cells, on mice with both human bone marrow and human cancers —either multiple myeloma or melanoma—and studied what happened to the mice's immune systems, the cancers, and the HSC-iNKT cells after they had integrated into the bone marrow.

They found that the stem cells differentiated normally into iNKT cells and continued to produce iNKT cells for the rest of the animals' lives, which was generally about a year. "One advantage of this approach is that it's a one-time cell therapy that can provide patients with a lifelong supply of iNKT cells," Yang said.

While mice without the engineered stem cell transplants had nearly undetectable levels of iNKT cells, in those that received engineered stem cell transplants, iNKT cells made up as much as 60% of the immune systems' total T cell count. Plus, researchers found they could control those numbers by how they engineered the original hematopoietic stem cells.