Early reports underscore both the therapeutic potential and the major challenges that remain, including on-target/off-tumor toxicity due to NKG2D ligand expression on normal tissues, as well as adverse immune-mediated events such as cytokine release syndrome (CRS) and neurotoxicity (ICANS, replacing the outdated “NTS” abbreviation). This evidence concerns the gene KLRK1 and congenital rubella syndrome.