Scientists from MIT and Harvard have developed engineered CAR-NK immune cells that evade the body's defenses to target cancer effectively. This advancement could enable off-the-shelf treatments available immediately after diagnosis, bypassing weeks of personalized cell production. The cells showed strong results in mouse tests, destroying most lymphoma cells without triggering severe side effects.
A team from MIT and Harvard Medical School has engineered CAR-NK cells, a type of natural killer cell modified to attack cancer while hiding from the host's immune system. These 'stealth' cells address a key limitation of cell-based therapies: rejection by the patient's own T cells and other immune components, which often reduces effectiveness.
The researchers created a single DNA construct incorporating a CAR to target CD-19 proteins on malignant B cells in lymphoma, along with siRNA to silence HLA class 1 genes—surface markers that flag cells as foreign—and genes for PD-L1 or single-chain HLA-E to boost anti-cancer activity. This one-step method converts donor NK cells into evasive, potent fighters.
In tests on mice with humanized immune systems and injected lymphoma cells, the engineered CAR-NK cells persisted for at least three weeks, nearly eliminating the cancer. Control groups receiving unmodified or partially modified NK cells saw donor cells destroyed within two weeks, allowing cancer to spread. The new cells also reduced the risk of cytokine release syndrome, a dangerous side effect of immunotherapies.
"This enables us to do one-step engineering of CAR-NK cells that can avoid rejection by host T cells and other immune cells. And, they kill cancer cells better and they’re safer," said Jianzhu Chen, an MIT professor of biology and senior author.
The study, led by Fuguo Liu, a postdoctoral researcher at the Koch Institute and Dana-Farber, was published in Nature Communications. Senior authors include Rizwan Romee from Harvard Medical School and Dana-Farber. The team plans clinical trials for lymphoma and is exploring applications for lupus with a biotech partner. Funding came from sources like the National Cancer Institute and the Koch Institute.