Good news! Impressive! Cancer is history (soon)!
"... have developed a new way to program natural killer (NK) immune cells to target cancerous T cells or T cells that have become autoreactive, leading to diseases such as lymphoma and autoimmune hepatitis.
Using their new technique, the researchers can reprogram NK cells to target diseased T cells without ever removing the NK cells from the patient’s body. Instead, they use lipid nanoparticles to deliver messenger RNA directly to NK cells. These mRNA molecules encode proteins that allow the NK cells to seek and destroy the dysfunctional T cells.
Known as CAR NK cells, these cells could be deployed against a variety of diseases. ...
To generate these cells, the ... team designed lipid nanoparticles (LNPs) that can deliver an mRNA payload. These strands of mRNA encode a CAR that can be targeted to specific cell types. For example, they could deliver a CAR that targets CD19, a protein found on B cells, or CD3, a protein found on autoreactive T cells.
The particles are coated with antibody fragments that bind to receptors found on the surface of NK cells, to ensure they reach the correct targets. ...
In a mouse model of an aggressive form of melanoma, three of the five mice that received LNPs that reprogrammed their NK cells to target the cancer cells went into complete remission. ...
The researchers also saw significant tumor destruction when they used the LNPs to treat T cell lymphoma in a humanized mouse model, created when mice receive transfusions of human blood cells, allowing them to transiently generate a human-like immune system.
In these mice, tumors were eradicated after five injections of the reprogramming LNPs. ..."
From the abstract:
"Targeted lipid nanoparticles (LNPs) offer a nonviral approach for in vivo cell engineering but efficient programming of natural killer (NK) cells remains underexplored.
Here we develop NK cell-targeted LNPs (NtLNPs) using engineered biparatopic NK cell ligands to drive receptor-specific uptake and mRNA delivery.
Lead NtLNPs achieve up to ~80% NK cell transfection with minimal off-target effects in mice.
Systemic delivery of chimeric antigen receptor (CAR) mRNA using NtLNPs generates CAR NK cells in vivo.
CD19-targeted CAR NKs completely deplete circulating B cells in healthy mice and CD3-targeted CAR NKs eliminate nearly all autoreactive T cells in an autoimmune hepatitis model, highlighting a potential advantage over CAR T therapies for T cell-driven disease.
CD19-targeted CAR NKs completely deplete circulating B cells in healthy mice and CD3-targeted CAR NKs eliminate nearly all autoreactive T cells in an autoimmune hepatitis model, highlighting a potential advantage over CAR T therapies for T cell-driven disease.
In solid tumors, NtLNPs targeting the inhibitory checkpoint NKG2A enhance antitumor efficacy by relieving Qa-1b-mediated immunosuppression.
Lastly, we optimized NtLNPs for in vivo engineering of human CAR NK cells, enabling regression of two humanized hematologic malignancy models and establishing NtLNPs as a modular immunotherapy system."
In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles (no public access)
Preprint paper not found for this article!
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