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Table 1 Preclinical trials of CAR-engineered NK cells

From: Renaissance of armored immune effector cells, CAR-NK cells, brings the higher hope for successful cancer therapy

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]
  1. 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