New cellular immunotherapy shows promise against solid tumors

Since the first FDA approval nearly a decade ago of a chimeric antigen receptor (CAR) T cell therapy, in which a patient’s own immune cells are genetically engineered to recognize and attack their cancer, scientists have been trying to design next-generation cellular immunotherapies that persist longer in the body and infiltrate solid tumors more effectively.

One strategy that has shown promise is engineering another type of immune cell—natural killer (NK) cells—rather than T cells. Since NK cells do not respond to all of the same threats as T cells, they carry a reduced risk of immune complications from therapy. CAR NK cells have, however, encountered the same challenges as CAR T cells against solid tumors, which until recently have resisted infiltration.

But this February, former Damon Runyon-Dale F. Frey Breakthrough Scientist Sidi Chen, PhD, and his colleagues at Yale University announced a major breakthrough. Using a cutting-edge genetic screening strategy, the team searched for genes that could give CAR NK cells a performance boost. One gene stood out: OR7A10, a gene not previously linked to cancer immunotherapy.

When researchers engineered CAR NK cells to express OR7A10, “all of a sudden these NK cells started to work against solid tumors,” reported Dr. Chen. The modified NK cells multiplied more efficiently, attacked cancer cells more actively, and resisted exhaustion. They were also better equipped to survive in the tumor microenvironment and persist over time, two of the biggest barriers to success against solid tumors. In mouse models of breast, colon, and ovarian cancers, the engineered cells produced a stronger anti-tumor response than standard CAR NK cells, and in one breast cancer model, the therapy produced complete tumor responses in every treated animal.

“We really believe this type of therapy has immense potential in patients,” Dr. Chen told his institution.

Further, because OR7A10 can be added using a simple, scalable manufacturing approach, this strategy opens the door to an “off-the-shelf” immune cell therapy that could be produced in advance and made broadly available to patients.

This research was published in Nature.