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Table 2 Overview of in vivo 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 results

Ref

B cell malignancies

CD19

Prolonged survival in a xenograft Raji lymphoma murine model upon injection iC9/CAR.19/IL-15-transduced CB NK cells which produce IL-15 to improve their function

[148]

B cell precursor acute lymphoblastic leukemia

CD19

Potent antileukemia activity of human lymphoma in (NSG) xenograft mice model by CAR-CD19-PB NK cells

[154]

B cell leukemia and lymphoma

CD19

Abrogation of disease progression with selective cytotoxicity against Raji B cell lymphoma xenograft NSG mice model upon injection of NK-92/63.z cells

[64]

B cell acute lymphoblastic leukemia (BLL)

CD19

Complete molecular remission and prolonged survival in B cell lymphoma xenograft (NSG) mice model by CD19-CAR-NK cells

[155]

Lymphoma and leukemia

CD19 & CD20

Eradication of TMD-5 (CD19 + CD20+) cells by Intrafemoral injection of CD19-CAR NK-92 and eliminating BCR-ABL1+ SUP-B15 (CD19 + CD20−) cells by intravenous injection of CD19-CAR NK-92 in xenotransplant mouse models

Effective suppressing local tumor development in Daudi lymphoma xenograft mice model by CD20-CAR NK-92 than CD19-CAR NK-92

[158]

B cell non-Hodgkin’s lymphomas (NHL)

CD20

Inhibiting MAVER-1 tumor cell growth in xenograft NCG mice model with NK- 92MI cells expressing receptor of CD16-BB-ζ

[159]

CD20+ B cell non-Hodgkin’s lymphomas (NHL)

CD20

Reducing tumor size and extended survival in Raji-Luc and Raji-2R-Luc xenograft NSG mice model upon injection of CD20-CAR-PB NK cells

[160]

Burkitt Lymphoma

CD20

The combination of romidepsin and CD20-CAR-PB NK cells reduced tumor burden and enhanced survival in humanized BL in xenograft NSG mice models

[161]

Pre-B cell acute lymphoblastic leukemia (B-ALL)

FLT3

Abrogated disease progression, high antileukemic activity, and enhancing safety by NK-92 cells co-expressing the FLT3-specific CAR and iCasp9 in a B-ALL xenograft model in NSG mice

[162]

T cell acute lymphoblastic leukemia

CD5

Abrogated disease progression and improved survival with CD5-CAR-NK-92 cells in xenograft mouse models of CD5+ T-ALL

[163]

T cell malignancies

CD5

A significant decrease in tumor burden was observed with CD5-CAR-expressing NK-92 cells in a T cell leukemia xenograft mouse model

[164]

T cell malignancies

CD5

CD5-CAR-NK cells with costimulators 2B4 showed superior cytotoxic ability against T-ALL in mouse xenograft models and prolonged the survival of T-ALL xenograft mice than CD5-CAR-NK with costimulators 4-1BB

[98]

T cell non-Hodgkin’s lymphomas (NHLs)

CD4

CD4-CAR-NK-92 cells significantly reduced tumor burden and prolonged survival in KARPAS-299-injected NSG mice

[165]

Multiple myeloma

CS1

Suppressing the growth of human IM9 MM cells and also significantly prolonged survival in an aggressive orthotopic MM xenograft mouse model upon injection of CS1-CAR-NK-92 cells

[166]

Multiple myeloma

CD138

Marked antitumor activity toward CD138+ MM cells in the xenograft SCID mouse model by CD138-CAR-NK-92MI cells

[167]

Acute myeloid leukemia (AML)

CD123

Significantly reduced disease burden in NSG mice xenografted with luciferase-expressing THP-1 cells upon injection of CD123-CAR-NK-92

[171]

Acute myeloid leukemia (AML)

CD4

Antileukemic effects in a systemic AML murine model with CD4-CAR-PB NK cells

[173]