Reprogrammed NK immune cells target cancer and autoimmune disorders.
MIT engineers developed lipid nanoparticles that deliver mRNA to natural killer cells inside the body, reprogramming them to attack cancerous or autoreactive T cells in mouse experiments.
MIT engineers have developed a way to program natural killer (NK) immune cells to target cancerous T cells, or T cells that have become autoreactive and drive diseases such as lymphoma and autoimmune hepatitis. The study appeared in Nature Biotechnology. Daniel Anderson, a professor of chemical engineering at MIT, is the senior author. The lead authors are postdoc Yuang Chen and graduate students Julia Monkovic and Haseeb Mughal, and Robert Langer is also an author.
The method reprograms NK cells without removing them from the patient. Lipid nanoparticles carry messenger RNA that encodes a chimeric antigen receptor (CAR), which lets the cells find and destroy a chosen target. The particles are coated with antibody fragments that bind to receptors on NK cells, which directs them to the right cells. The CAR can be aimed at CD19, a protein on B cells, or at CD3, a protein found on autoreactive T cells.
CAR T cell therapies are made by taking blood from a patient, engineering the cells in a lab and infusing them back. CAR NK cells are made in a similar way, and no CAR NK therapy is yet FDA approved. The researchers say NK cells could be useful against T cell diseases because CAR T cells aimed at T cell proteins may end up killing one another. Anderson said an infusion of nanoparticles could "dramatically simplify the process and reduce costs."
In mice, the nanoparticles reprogrammed about 80 percent of the targeted NK cells. In a mouse model of aggressive melanoma, three of five treated mice went into complete remission. In a humanized mouse model of T cell lymphoma, tumors were eradicated after five injections, similar to the result with CAR NK cells made by the conventional approach of removing, reprogramming and returning them.
In mice with autoimmune hepatitis, the autoreactive T cells were destroyed and liver damage healed after a single injection. The team hopes engineered NK cells could eventually be used against other T cell-driven autoimmune disorders, including multiple sclerosis and rheumatoid arthritis. All results reported on the page come from mouse models. Funding came from Sanofi, the Marble Center for Cancer Nanomedicine and a National Cancer Institute core grant to the Koch Institute.
At a Glance
- The nanoparticles reprogrammed about 80 percent of targeted NK cells in mice, according to the MIT researchers.
- Three of five melanoma-model mice went into complete remission after receiving the NK-reprogramming nanoparticles.
- Lymphoma tumors in humanized mice were eradicated after five injections, similar to conventionally made CAR NK cells.
- One injection destroyed autoreactive T cells and healed liver damage in mice with autoimmune hepatitis.
- No CAR NK cell therapies are currently FDA approved, though the FDA has approved seven CAR T cancer treatments.
Sources
This brief was written by Brightside Report from the reporting linked above. Spot an error? Request a correction.