NK cells carry a second advantage. Using engineered T cells against T cell diseases often backfires, because the engineered T cells recognize each other's proteins and kill one another alongside the diseased cells. NK cells don't have that problem.

"NK cells can treat these T cell malignancies — not only T cell cancer, but also T cell autoimmune diseases," said lead author Yuang Chen, an MIT postdoc.

How does the delivery work?

The researchers packaged mRNA strands — molecular instructions that cells read to build proteins — inside lipid nanoparticles, tiny fatty shells similar to those used in mRNA vaccines. Each particle is coated with antibody fragments that latch onto receptors on the surface of NK cells, steering the payload to the right target.

Once delivered, the mRNA directs the NK cells to build CAR proteins aimed at specific cell types. In one configuration, the CAR targets CD3, a protein found on autoreactive T cells; the team also demonstrated a version targeting CD19, a protein on B cells.

"If a patient can just get an infusion of nanoparticles, it would dramatically simplify the process and reduce costs," Anderson said.

What did the mouse studies show?

The results, while early and so far limited to mice, were striking across three disease models:

• In a mouse model of aggressive melanoma, three of five mice that received the reprogramming nanoparticles went into complete remission.
• In a humanized mouse model of T cell lymphoma — mice given human blood cells so they transiently develop a human-like immune system — five injections eradicated the tumors, matching results from conventionally manufactured CAR NK cells.
• In mice with autoimmune hepatitis, where T cells attack liver cells, a single injection destroyed the autoreactive T cells and the liver damage healed.

"This study is an excellent example of the power of nano delivery systems and their ability to potentially treat cancer and other diseases," said Robert Langer, the David H. Koch Institute Professor at MIT and a co-author of the paper.

What comes next?

The findings are preliminary. All the results come from mice, and no CAR NK cell therapy has yet received FDA approval, though many research groups are pursuing them for cancer and autoimmune disorders. The MIT team, which also included graduate students Julia Monkovic and Haseeb Mughal, hopes the approach could eventually treat autoimmune disorders driven by dysfunctional T cells, including multiple sclerosis and rheumatoid arthritis.

Sanofi, the Marble Center for Cancer Nanomedicine and a Koch Institute Support Grant from the National Cancer Institute funded the research.