Table 2.
Current genetic engineering strategies aimed at improving the functions of NK cells.
| Cell Source | Modifications | Transduction | Model | Malignancy | Ref. |
|---|---|---|---|---|---|
| NK-92 | CD16(158V): CD16(allotype-V158)-CD8-4-1BB-CD3ζ | LV | None | Multiple cancers | [122] |
| NK-92, iPSC-NK |
CD16a/S197P: convert the serine at position 197 to a proline in CD16 | RV, SB transposon |
None | - | [171] |
| iPSC-NK | hnCD16: high-affinity CD16a 158V variant | SB transposon | B-cell lymphoma/OC CDX model in NSG mice | Multiple cancers | [98] |
| NK-92, iPSC-NK |
CD64/16a: CD64 ECD-CD16(TM + ICD) | RV, SB transposon |
None | - | [172] |
| NK-92MI | CD64 | RV | mCRPC CDX model in NSG mice | mCRPC | [173] |
| NK-92 | TCR: hCD3(CD3γ/δ/ε/ζ dimers)-TCR (TCRα/β) | RV | CRC CDX model in NSG mice | CRC | [174] |
| NK-92, YTS |
TCR: hCD3(CD3γ/δ/ε/ζ dimers)-TCR (TCRα/β) | LV | Melanoma CDX model in NOD/SCID mice | Melanoma | [175] |
| NK-92 | CD22 ligand | Glycoengineering | B cell lymphoma CDX model in Balb/c nude mice | B cell lymphoma | [176] |
| NK-92MI | CD22 ligand and selectins | Glycoengineering | B cell lymphoma CDX model in NSG mice | B cell lymphoma | [126] |
| PB-NK | TGFBR2 knockout | CRISPR/Cas9 | GBM PDX model in NSG mice | GBM | [177] |
| NK-92 | SMAD3-silencing | LV | Hepatoma and melanoma CDX model in NOD/SCID mice | Hepatoma and melanoma | [178] |
| CB-NK | Variant TGF-β receptors: (RBDNR: TGF-βRII-truncated CD19-Puro; NKA: TGF-βRII-DAP12-truncated CD19-Puro; NKCT: TGF-βRII-synNotch-RELA-truncated CD19-Puro) | RV | Neuroblastoma CDX model in NSG mice | Neuroblastoma | [179] |
| PB-NK | CBLB knockout | CRISPR/Cas9 | AML CDX model in NSG mice | - | [180] |
| NK-92 | DNAM-1 and NKG2D | LV | None | Sarcomas | [181] |
| PB-NK | Gain-of-function variant CXCR4R334X | Electroporation | NSG mice | - | [182] |
| iPSC-NK | CISH knockout | CRISPR/Cas9 | AML CDX model in NSG mice | AML | [97] |
| NK-92, PB-NK |
EPOR or c-MPL | LV | NSG mice | - | [183] |
| PB-NK | CD38 knockout | CRISPR/Cas9, Electroporation |
NSG mice pretreated with DARA | MM | [184] |
| PB-NK | CD38 knockout and CD16 (158V) | CRISPR/Cas9, Electroporation |
MM CDX model in NSG mice | MM | [185] |
PB, peripheral blood; CB, cord blood; iPSC, induced pluripotent stem cell; ECD, extracellular domain; TM, transmembrane; ICD, intracellular domain; TCR, T cell receptor; LV, lentivirus; RV, retrovirus; SB, sleeping beauty; mCRPC, metastatic castration resistant prostate cancer; OC, ovarian cancer; CRC, colorectal cancer; GBM, glioblastoma multiforme; AML, acute myeloid leukemia; MM, multiple myeloma.