Table 1.
Preclinical trials of CAR-engineered NK cells
| Hematological malignancies | |||||
|---|---|---|---|---|---|
| Target | Malignancy | Signaling domain | Source of NK cells | Genetic modification method | Reference |
| CD19 | B cell acute lymphoblastic leukemia (B-ALL)/B cell malignancies | CD28 + CD3ζ | Primary human NK cells from PBMCs | Lentiviral transduction | [168] |
| CD19 | B cell acute lymphoblastic leukemia (B-ALL)/B cell malignancies | 2B4 + CD3ζ | Primary human NK cells from PBMCs | retroviral transduction | [165] |
| CD19 | B cell acute lymphoblastic leukemia (B-ALL)/B cell malignancies | 4-1BB + CD3ζ | Primary human NK cells from PBMCs | mRNA electroporation | [128] |
| CD19 | (B-ALL) and non-Hodgkin lymphoma (NHL)/B cell malignancies | 4-1BB + CD3ζ | Primary human NK cells from PBMCs | mRNA electroporation; retroviral transduction | [129] |
| CD19 | B-ALL cells/ B cell malignancies | 4-1BB/CD3ζ | Primary human NK cells from PBMCs | Trogocytosis | [134] |
| CD19 | B cell malignancies | CD3ζ | UCB | Retroviral transduction | [55] |
| CD19 | B cell malignancies | CD3ζ | NK-92 cells | Retroviral transduction | [76] |
| CD19 | CLL/ B cell malignancies | CD3ζ | NK-92 cells | mRNA electroporation | [75] |
| CD19 | B cell malignancies |
CD3ζ CD28 + CD3ζ 4-1BB + CD3ζ |
NK-92 cells | Lentiviral transduction | [169] |
| CD19 | CD20 resistant non-Hodgkin lymphoma (bNHL) | CD28 + CD3ζ | NK-92 cells | NR | [141] |
| CD20 | B cell malignancies non–Hodgkin lymphoma (bNHL) | 4-1BB + CD3ζ | Primary human NK cells from PBMCs | mRNA electroporation | [170] |
| CD20 | B cell malignancies | CD3ζ | NK-92 cells | Retroviral transduction | [140] |
| CD19 and CD20 | B cell malignancies | CD3ζ | NK-92 cells | Lentiviral transduction | [171] |
| CS1 | Multiple myeloma | CD28 + CD3ζ | NK-92 cells | Lentiviral transduction | [145] |
| CD138 | Multiple myeloma | CD3ζ | NK-92MI cells | Lentiviral transduction | [146] |
| FLT3 | B-ALL/B cell malignancies | CD28 + CD3ζ | NK-92 cells | Lentiviral transduction | [142] |
| CD5 | T cell malignancies | CD28 + 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [73] |
| CD5 | T cell malignancies | CD28 + CD3ζ | NK-92 cells | Lentiviral transduction | [172] |
| CD3 | T cell malignancies | CD28 + 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [98] |
| CD4 | T cell malignancies | CD28 + 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [143] |
| EBNA3C | EBV-positive T cells | 4-1BB + CD3ζ | NK-92MI cells | Retroviral transduction | [173] |
| Solid tumors | |||||
| GD2 | Ewing sarcoma | CD28 + 4-1BB + CD3ζ | Primary human NK cells from PBMCs | Retroviral transduction | [167] |
| GD2 | Neuroblastoma | CD3ζ | NK-92 cells | Retroviral transduction | [166] |
| GD2 | Neuroblastoma | 2B4 + CD3ζ | Primary NK cells from PBMC and NK-92 cells | Retroviral transduction | [165] |
| EpCAM | Breast cancer | CD28 + CD3ζ | NK-92 and NKL cells | Lentiviral transduction | [174] |
| EpCAM | Colorectal cancer | 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [162] |
| Carbonic Anhydrase IX (CAIX) | Renal cell carcinoma (RCC) | CD28 + 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [175] |
| PSCA | Prostate cancer/PSCA+ tumor cells | DAP12 | Primary human NK cells from PBMCs and YTS cells | Lentiviral transduction | [80] |
| GPA7 | Melanoma | CD3ζ | NK-92 cells | mRNA electroporation | [176] |
| GPC3 | Hepatocellular carcinoma (HCC) | CD28 + CD3ζ | NK-92 and Primary human NK cells from PBMCs | Lentiviral transduction | [177] |
| CEA | Colorectal cancer | CD3ζ | NK-92MI cells | Retroviral transduction | [178] |
| EGFR, EGFRvIII | Glioblastoma multiform (GBM) | CD28 + CD3ζ | NK-92 and NKL and Primary human NK cells from PBMCs | Lentiviral transduction | [130, 148] |
| EGFRvIII | Glioblastoma | DAP12 | YTS cells | Lentiviral transduction | [78] |
| NKG2D | Osteosarcoma; prostate, colon, HCC, and breast cancer (NKG2D) | DAP10 + CD3ζ | Primary NK cells from PBMC | Retroviral transduction | [179] |
| NKG2D | CD73+ solid tumors /lung cancer | DAP10 + CD3ζ | NK-92 cells | PiggyBac transposon | [137] |
| NKG2D | Ovarian cancer | 2B4 + CD3ζ | iPSC-derived human NK cells | PiggyBac transposon | [102] |
| ErbB2/HER-2 | Breast/ovarian cancer/squamous cell carcinoma | CD3ζ | NK-92 cells | Retroviral transduction | [158] |
| ErbB2/HER-2 | Ovarian and breast cancer | CD28 + CD3ζ | Primary NK cells from PBMC | Retroviral transduction | [180] |
| ErbB2/HER-2 | Breast cancer/renal cell carcinoma (RCC) | CD28 + 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [159] |
| ErbB2/HER-2 | Glioblastoma | CD28 + CD3ζ | NK-92 cells | Lentiviral transduction | [149] |
| ErbB2/HER-2 | Breast cancer | CD28 + CD3ζ | NK-92 cells | mRNA electroporation | [181] |
| EGFR | Renal cell carcinoma (RCC)/solid tumor | CD28 + 4-1BB + CD3ζ | NK-92 cells | Lentiviral transduction | [182] |
| EGFR | Breast cancer brain metastases | CD28 + CD3ζ | Primary NK cells from PBMC and NK-92 cells | Lentiviral transduction | [164] |
EGFR epidermal growth factor receptor, HCC hepatocellular carcinoma, PBMC peripheral blood mononuclear cell, CEA carcinoembryonic antigen, RCC renal cell carcinoma, CAIX carbonic anhydrase IX, UCB umbilical cord blood