Table 1 Overview of in vitro studies based on CAR-NK cell therapy for hematological malignancies
From: CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies
Condition | Target | Main outcomes | Ref |
|---|---|---|---|
B cell acute lymphoblastic leukemia (ALL) and T cell ALL | NKG2D | Secretion of IFN-γ, GMCSF, IL-13, MIP-1a, MIP-1b, CCL5, and TNF-ɑ, massive release of cytotoxic granules and efficient cytotoxic effects against T cell ALL (CEM-C7, MOLT-4, Jurkat) and B cell ALL (REH, OP-1) by NKG2D-DAP10-CD3z-expressing NK cells | [152] |
B cell malignancies | CD19 | The efficient killing of CD19-expressing cell lines and primary leukemia cells by iC9/CAR.19/IL-15-transduced cord blood (CB)-NK cells | [148] |
B cell ALL and B cell chronic lymphocytic leukemia (CLL) | CD19 | Higher anticancer activity of peripheral blood (PB)- CAR-NK cells compared with CB CAR-NK cells at killing CD19+ K562, Nalm-6 target cells, and ALL and CLL cells | [153] |
B cell leukemia and lymphoma | CD19 | Exposure of established cancer cell lines and primary pre-B-ALL blasts with NK-92/63.z and NK-92/63.28.z cells led to cell killing and cytokine production | [64] |
B cell precursor acute lymphoblastic leukemia | CD19 | Higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B cell precursor ALL with CAR-CD19-PB NK cells | [154] |
B cell acute lymphoblastic leukemia (BLL) | CD19 | Specific cell killing activity against CD19-expressing Raji Burkitt’s lymphoma and primary B-ALL blasts by CD19-CAR-NK cells | [155] |
Chronic lymphocytic leukemia (CLL) | CD19 | Significant cytolytic function toward previously resistant CD19 positive cell lines and primary CLL cells by CD19-CAR-NK-92 cells | [156] |
NK-resistant B cell lymphoma malignancies | CD19 | Displaying significantly increased IFN-γ production, degranulation, and specific killing against NK-resistant lymphoma lines and primary targets by CD19-CAR-NK cells | [157] |
Lymphoma and leukemia | CD20 | Effective eliminating NK cell-resistant primary CLL by CD20-CAR-NK-92 cells | [158] |
B cell non-Hodgkin’s lymphomas (NHL) | CD20 | Improved cytotoxicity against rituximab-opsonized Raji and MAVER-1 CD20+ cell lines by NK-92MI cells expressing CD16-BB-ζ or CD64- BB-ζ receptors | [159] |
CD20+ B- non-Hodgkin’s lymphomas (NHL) | CD20 | Marked cytotoxicity against CD20+ Ramos, Daudi, Raji, and two rituximab-resistant cell lines (Raji-2R and Raji-4RH) by CD20-CAR PB NK cells | [160] |
Burkitt Lymphoma | CD20 | The combined treatment with romidepsin and CD20-CAR-PB NK cells significantly induced cell death in Burkitt Lymphoma cell lines such as Raji, Raji-2R, and Raji-4RH cells | [161] |
pre-B cell acute lymphoblastic leukemia (B-ALL) | FLT3 | Exposure of FLT3-positive B-ALL cell lines and primary blasts with CAR NK-92 cells resulted in NK-cell degranulation and selective cytotoxicity | [162] |
T cell leukemia and lymphoma | CD5 | Eliminating both CD5+ tumor cell lines and CD5+ primary tumor cells in vitro by CD5-CAR-NK-92 cells | [163] |
T cell malignancies | CD5 | Notable cytotoxicity against the CD5-positive Jurkat and MOLT-4 leukemia cells by CD5-CAR-expressing NK-92 cells | [164] |
T cell malignancies | CD5 | CD5-CAR-NK cells with costimulators 2B4 displayed greater anti-CD5+ cytotoxicity than CD5-CAR-NK with costimulators 4-1BB against CD5+ malignant cell lines, and primary CD5+ malignant cells through upregulation of activation markers and cytotoxic granule release | [98] |
T cell non-Hodgkin’s lymphomas (NHLs) | CD4 | Robustly eliminating diverse CD4+ human T cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and primary CD4+ T cell malignancies by CD4-CAR-NK-92 cells | [165] |
Multiple myeloma | CS1 | Improved cytotoxicity against CS1+ MM cell lines and IFN-γ production with CS1-CAR-NK-92 and CS1-CAR-NK cells | [166] |
Multiple myeloma | CD138 | Significant cytotoxicity and secretion of granzyme B, IFN-γ, and proportion of CD107a expression in CD138-CAR-NK-92MI cells in response to CD138-positive human MM cell lines (RPMI8226, U266, and NCI-H929) | [167] |
Multiple myeloma | NKG2D | Primary NK cells from MM patients transduced with NKG2D-CARs showed considerably cytotoxic activity against the majority of MM cell lines | [168] |
Acute myeloid leukemia (AML) | CD123 | Recognition of CD123 + AML cell line KG1a and primary AML blasts and enhanced secretion of TNF-ɑ, IFN-γ and granzyme A and B along with showing significant cytotoxicity against listed cell lines | [169] |
Acute myeloid leukemia (AML) | CD123 | More prominent cytotoxic activity and secreting higher granzyme A and IL-17A levels against the CD123+ AML cell line KG-1a and primary human AML cells by CAR-NK-92 than CAR-PB NK | [170] |
Acute myeloid leukemia (AML) | CD123 | Cytolytic functions in association with perforin and granzyme production against CD123 expressing AML cell lines upon exposure with CD123 CAR-NK-92 | [171] |
Acute myeloid leukemia (AML) | CD123 | CD123-CAR-CB NK cells showed more antileukemic activity and higher secretion of TNF-ɑ, IFN-γ against CD123+ AML cell lines (THP-1 and MOLM-14) | [172] |
Acute myeloid leukemia (AML) | CD4 | Elimination of CD4+ AML cell lines THP-1, U937, and MOLM-13 and CD4+ human primary AML cells by CD4-CAR-PB NK cells | [173] |