#Cell_Therapies NK Cells

A look at NK cell therapies.
1/ NK cells are a close cousin to the cytotoxic T cell so it is only logical that scientists would look at them for use in cell therapies to treat cancer. They use the same cytotoxic mechanisms to kill infected or defective cells.
2/ There are some major difference between the CD8+ T cells and the NK cell. The first is the NK cell does not use MHC I the same as the T cell. The cytotoxic T cell reads the MHC I on the cell along with any antigens it is presenting. It works with the MHC I.
3/ NK cells read the level of MHC I on the surface using sets of activating and inhibitors receptors on its surface like NKG2D and KIR. The NK cell activates when MHC I is missing. Image
4/ Many infected or tumor cells will stop producing MHC I to protect themselves from the T cell. The NK cell is designed to detect this and kill those cells that lack MHC I expression.
5/ The combination of the Cytotoxic T cell and the NK cell are like the dynamic duo that regulate the 2 aspects of MHC I expression on cells. One activates in its presence while the other activates in its absence.
6/ When using a NK cell to do CAR-NK, you can easily leave these receptors active as they can still do their jobs without any problems unlike the original TCR receptor for the T cells. Image
7/ One of the major benefits of using NK cells over T cells is they produce much lower levels of pro inflammatory cytokines which lead to a lot of the toxicities of the CAR-T therapies like CRS and nuerotoxicity.
8/ NK cells do tend to be less robust and don't last as long as the T cells. The data so far has show to be lower on responses and durability. It is still early though.
9/ Another major advantage is the NK cell has the CD16 receptor with allow them to work with antibodies in a process called Antibody Dependent Cellular Cytotoxicity (ADCC). This allows for great combination treatments with already existing and newly developed cancer antibodies. Image
10/ With a NK cell, you don't have to worry about knocking out PD-1 as it does not effect them. That saves you an edit.
11/ They still display MHC I of their donor as they are still cells. This can be fixed the same as with T cells by doing the knock out and replacement of the MHC I on the NK cell. They can replace it with HLA-E or equivalent.

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