Fig. 1.

The fundamentals of CAR engineering of three generations of CAR-NK cells. CAR molecules on NK cells consist of three main parts: an antigen detection domain (e.g., ScFv), a transmembrane domain, and the signaling domain. First-generation CARs consist of CD3ζ as the signaling domain. Second-generation CARs have the CD-28 or a combination of CD-28 and a second additional signaling molecule: 4-1BB. As an example of 3rd generation, a CAR comprising an activating receptor; NKG2D can be constructed containing the signaling molecules: CD3ζ and DAP10/12. It was found that CD3ζ has better signaling properties than DAP10 and also it seems that DAP12 may activate NK cells better than both CD3ζ and DAP10. NK cells antigen binding or receiving activation signal by a bunch of activator receptors such as NKG2D leads to signal transduction, NK cell activation, the release of cytolytic enzymes, cytokine production, and also NK cells expansion and maintenance