Table 2.
CAR-NK cells that have been evaluated preclinically
| Target | CAR construct(s) | Source of NK | Method(s) | Cancer type(s) | References |
|---|---|---|---|---|---|
| Hematological cancers | |||||
| CD19 |
CD19-scFv-CD3ζ, CD19-scFv-CD28-CD3ζ, CD19-scFv-41BB-CD3ζ, CD19-scFv-DAP10-CD3ζ, (iC9*).CD19-scFv.CD28-CD3ζ-(IL15*) |
NK-92, NKL, Cord Blood, peripheral blood | Retrovirus, lentivirus | B cell malignancies | [38, 39, 49, 52, 63] |
| FLT3 | FLT3-scFV-CD28-CD3ζ | NK-92 | Lentivirus | B cell acute lymphoblastic leukemia (B-ALL) | [62] |
| CS1 | CS1-scFv-CD28-CD3ζ | NK-92 | Lentivirus | Multiple Myeloma | [53] |
| CD38 | Nb(CD38)a-CD28-41BB-CD3ζ | NK-92 (with CD38 knocked out) | Retrovirus | Multiple Myeloma | [72] |
| CD4 | CD4-scFv-CD28-41BB-CD3ζ | NK-92 | Lentivirus | Peripheral T cell lymphoma | [73] |
| CD5 | CD5-scFv-2B4-CD3ζ | NK-92 | Lentivirus | T cell malignancies | [46] |
| CD7 | Nb(CD7)-CD28-41BB-CD3ζ | NK-92MI | PiggyBac Transposon System | T cell acute lymphoblastic leukemia (T-ALL) | [67] |
| Solid cancers | |||||
| Wild Type EGFR and/or EGFRvIII |
EGFR-scFv-CD28-CD3ζ, EGFR-scFv-CD28-41BB-CD3ζ, EGFRvIII-scFv-CD28-CD3ζ, EGFRVIII-scFv-DAP12 |
NK-92 NKL, YTS |
Lentivirus | Glioblastoma, renal cell carcinoma, breast cancer | [47, 51, 58, 59, 71, 76] |
| ErbB2/HER2 |
ErbB2-scFv-CD3ζ, ErbB2-scFv-CD28-CD3ζ, ErbB2-scFv-41BB- CD3ζ |
NK-92 | Lentivirus, Retrovirus | Breast carcinoma, glioblastoma | [48, 60, 70] |
| GD2 | GD2-scFv-CD3ζ | NK-92 | Retrovirus | Neuroblastoma, melanoma, breast carcinoma | [65] |
| Glypican-3 (GPC3) |
GPC3-scFv-CD28-41BB-CD3ζ, GPC3-scFv-CD3ζ, GPC3-scFv-CD28-CD3ζ, GPC3-scFv-DNAM1-CD3ζ, GPC3-scFv-DNAM1-2B4-CD3ζ |
iPSC, NK-92 | Lentivirus | Ovarian cancer, hepatocellular cancer | [57, 66] |
| EpCAM |
EpCAM-scFV-41BB-CD3ζ, EpCAM-scFv-CD28-CD3ζ |
NK-92 | Lentivirus | Colorectal Cancer | [47, 50, 61] |
| Mesothelin |
Mesothelin-scFv-(NKG2D*)b-2B4-CD3z, Mesothelin-scFv-CD28-41BB-CD3ζ |
NK-92, iPSC | PiggyBac Transposon System; Lentivirus | Ovarian cancer | [42, 75] |
| Prostate Stem Cell Ag (PSCA) | PSCA-scFv-DAP12 | YST cell line, primary NK | Lentivirus | Prostate Cancer | [55] |
| Carcinoembryonic antigen (CEA) | CEA-scFv-CD3ζ | NK-92MI | Retrovirus | Colorectal Cancer | [69] |
| CD133 | CD133-CD28-41BB-CD3ζ | NK-92 | Lentivirus | CD133 + cancer stem cells, ovarian cancer | [64] |
| c-MET | c-MeT-scFv-41BB–DAP12 | Peripheral blood | Lentivirus | Liver cancer | [56] |
| NKG2D ligands |
NKG2D-CD3ζ, NKG2D-CD28- CD3ζ, NKG2D-CD28-41BB-CD3ζ, NKG2D-DAP10-CD3ζ |
Peripheral blood, NK-92 | RNA electroporation, PiggyBac Transposon System | NKG2DL + cancer cells, Ovarian cancer | [43, 44, 54] |
| PD-L1 | PD1-(NKG2D*)c-41BB | NK-92 | Lentivirus | PD-L1 + tumor cells | [68] |
| Tissue Factor (TF) | Factor VII light chain (FvIIL)-CD28-41BB-CD3ζ | NK-92MI (transduced to express CD16) | Lentivirus | Triple-negative breast cancer | [74] |
For CAR constructs, only the antigen recognition domain and signaling domain(s) are listed unless otherwise specified. Other functional domains will be in parentheses and marked by asterisks (*). Abbreviations: scFv = single-chain variable fragment; FLT3 = FMS-like tyrosine kinase 3;
aNanobody for CD38
btransmembrane domain of NKG2D
chinge region and transmembrane domain of NKG2D