MIT scientists have created a method to convert immune cells into cancer fighters directly inside the body, using lipid nanoparticles to deliver mRNA instructions to natural killer (NK) cells. This approach, described in a study published in Nature Biotechnology, could bypass the complex, time-consuming process of engineering CAR NK cells outside the body. In mouse models, three of five treated mice with aggressive melanoma experienced complete remission; tumors were eliminated in humanized mice with T cell lymphoma after five injections, while liver tissue healed after one injection in mice with autoimmune hepatitis.
The research focuses on natural killer cells, a type of immune cell that can be programmed to recognize and destroy harmful cells, including cancerous T cells and T cells that mistakenly attack healthy tissue. Current CAR T cell therapies require genetically modifying T cells from a patient's blood in a laboratory, which is expensive and labor-intensive. Additionally, using CAR T cells against T cell malignancies can cause the engineered cells to attack each other.
To overcome these limitations, the MIT team designed lipid nanoparticles (LNPs) coated with antibody fragments that target NK cells. These nanoparticles deliver mRNA instructions for producing chimeric antigen receptors, which direct the NK cells to specific targets. Senior author Daniel Anderson said, “The manufacturing challenges with CAR NK cells are significant. The idea here is you can deliver a nanoparticle that will modify your own NK cells with a CAR construct and teach them to attack tumor cells.”
In experiments, the technique successfully modified about 80 percent of targeted NK cells in mice. In animals with aggressive melanoma, three out of five treated mice experienced complete remission. Against T cell lymphoma in humanized mice, five injections completely eliminated tumors. In another test, a single injection of nanoparticles that instructed NK cells to target autoreactive T cells in mice with autoimmune hepatitis was followed by healing of damaged liver tissue.
“This study is an excellent example of the power of nano delivery systems,” said Robert Langer. Lead authors include Yuang Chen, Julia Monkovic, and Haseeb Mughal.
The researchers hope to extend the technology to conditions like multiple sclerosis and rheumatoid arthritis. Further research is needed to determine its safety and efficacy in humans.
Analysis
Why This Matters
- The technique could significantly reduce the cost and complexity of engineered immune cell therapies, making them more accessible to patients.
- It offers a potential treatment for T cell cancers and autoimmune diseases, which are difficult to target with current CAR T cell therapies due to the risk of engineered T cells attacking each other.
- A single injection reversed autoimmune liver damage in mice, suggesting the approach could be applied to a wide range of immune-related conditions.
Background
Current cancer immunotherapies like CAR T cell therapy require extracting immune cells from patients, modifying them in a lab, and reinfusing them. This process is expensive, time-consuming, and requires specialized equipment, which has limited their use primarily to blood cancers. Natural killer (NK) cells offer an alternative because they can be engineered to target T cell malignancies without the risk of engineered T cells attacking each other. However, producing CAR NK cells outside the body faces similar manufacturing challenges. The MIT team’s in vivo approach aims to bypass these steps by delivering genetic instructions directly to NK cells inside the body.
What to Watch
- Further research in humans will be needed to determine whether the technique is safe and effective.
- Expansion of the technology to treat other autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis, is a stated goal of the researchers.
- Continued funding and partnerships, such as support from Sanofi, will be critical for advancing the research toward clinical applications.
Checked
12 claims in this story checked against 1 source: 10 supported.
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- SupportedMIT researchers developed a nanoparticle technique to engineer cancer-fighting cells inside the body.Latest Science News -- ScienceDaily: “MIT researchers have developed a new technique that allows them to transform immune cells into cancer fighters directly inside the body”
- SupportedIn vivo reprogramming of NK cells could simplify CAR NK therapy.Latest Science News -- ScienceDaily: “By carrying out the engineering process inside the body, the new approach could eliminate much of the time, expense, and complexity involved in manufacturing personalized immune cell therapies.”
- SupportedThe method uses lipid nanoparticles to deliver mRNA instructions to NK cells.Latest Science News -- ScienceDaily: “The MIT team designed lipid nanoparticles (LNPs) capable of transporting messenger RNA into natural killer cells.”
- SupportedThe study was published in Nature Biotechnology.Latest Science News -- ScienceDaily: “Anderson is the senior author of the research, published in Nature Biotechnology .”
- SupportedThe approach could bypass the complex, time-consuming process of engineering CAR NK cells outside the body.Latest Science News -- ScienceDaily: “Producing CAR NK cells outside the body, however, still requires much of the specialized equipment, labor, and processing associated with CAR T cell manufacturing.”
- SupportedThree of five mice treated for aggressive melanoma experienced complete remission.Latest Science News -- ScienceDaily: “In mice with an aggressive form of melanoma, three of the five animals treated with nanoparticles designed to direct NK cells against the cancer experienced complete remission.”
- SupportedIn humanized mice with T cell lymphoma, five nanoparticle injections completely eliminated the tumors.Latest Science News -- ScienceDaily: “After five injections of the nanoparticles, the tumors were completely eliminated.”
- SupportedIn mice with autoimmune hepatitis, liver tissue healed after one nanoparticle injection.Latest Science News -- ScienceDaily: “These improvements occurred after just one nanoparticle injection, demonstrating the potential of the approach beyond cancer treatment.”
- SupportedDaniel Anderson said, “The manufacturing challenges with CAR NK cells are significant. The idea here is you can deliver a nanoparticle that will modify your own NK cells with a CAR construct and teach them to attack tumor cells.”Latest Science News -- ScienceDaily: “"The manufacturing challenges with CAR NK cells are significant. The idea here is you can deliver a nanoparticle that will modify your own NK cells with a CAR construct and teach them to attack tumor cells," says Daniel Anderson”
- Partly supportedRobert Langer said, “This study is an excellent example of the power of nano delivery systems.”Latest Science News -- ScienceDaily: “"This study is an excellent example of the power of nano delivery systems and their ability to potentially treat cancer and other diseases," Langer says.”
- SupportedThe technique modified about 80 percent of targeted NK cells in mice.Latest Science News -- ScienceDaily: “After injecting the nanoparticles into mice, the researchers successfully modified approximately 80 percent of the NK cells they were targeting.”
- Partly supportedCAR T cells used against T cell malignancies can attack each other.Latest Science News -- ScienceDaily: “Because both the engineered cells and their intended targets are T cells, the modified cells may recognize and destroy one another.”
