Table 1 Clinical trials of CAR-NK cell therapy in hematologic malignancies ^[1]

AML

NKX101

NKG2DL

Allogeneic NK cells

NCT04623944

I

Recruiting

To determine safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response. Preliminary results have shown striking early single-agent activity and no dose-limiting toxicities

NKX019

CD19

Allogeneic NK cells

NCT05020678

I

Recruiting

To evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response. Preliminary results showed that 3 of 6 patients achieved 50% CR

CAR.70/IL-15 transduced CB-NK cells

CD70

CB-NK cells

NCT05092451

I/II

Recruiting

To determine the safety, efficacy and optimal cell dose

Anti-CD33 CAR NK cells

CD33

Umbilical cord-NK cells

NCT05008575

I

Recruiting

To assess the safety and efficacy. 6 of 10 patients have received MRD-CR at day 28 assessment. 7 (70%) patients developed grade 1 CRS and only 1 patient developed grade 2 CRS

NKG2D

CAR NK cells

NKG2DL

CB-NK cells

NCT05247957

I

Recruiting

To explore the MTD, clinical safety and efficacy

Anti-CD33/CLL1 CAR NK cells

CD33

_

NCT05215015

Early I

Recruiting

To evaluate the safety, tolerability, PK, and efficacy. To determine MTD and phase II recommended dose

Anti-CD33 CAR NK cells

CD33

NK92 cells

NCT02944162

I/II

Recruiting

To determine safety and feasibility

Anti-CD123 CAR NK cells

CD123

Allogeneic NK cells

NCT05574608

Early I

Recruiting

A dose-escalation study to detect dose-limiting toxicity, incidence of AEs and disease response

Anti-CD7 CAR NK cells

CD7

Induced pluripotent stem cells

NCT02742727

I/II

Recruiting

To evaluate the safety and efficacy

ALL

CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells

CD19

CD28

CB-NK cells

NCT03056339

I/II

Active, not recruiting

To determine the safety and relative efficacy, assess the ORR. Of the 11 patients treated, 8 had a response including 7 (4 with lymphoma and 3 with CLL) had CR and 1 had remission, no major toxic effects were found

Anti-CD19 CAR NK cells

CD19

_

NCT05410041

I

Recruiting

To observe the safety and efficacy, and preliminarily evaluate the expansion of this product in vivo and the ORR after administration

Anti-CD19 CAR NK cells

CD19

_

NCT05563545

I

Recruiting

To observe the safety, dose tolerance and pharmacokinetic characteristics

Anti-CD19 CAR NK cells

CD19

CB-NK cells

NCT04796675

I

Recruiting

To evaluate the primary safety and efficacy

CLL

CAR.5/IL15-transduced CB-NK cells

CD5

CB-NK cells

NCT05110742

I/II

Not yet recruiting

To determine the safety, efficacy and optimal cell dose

CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells

CD19

CD28

CB-NK cells

NCT03056339

I/II

Active, not recruiting

To determine the safety and relative efficacy, assess the ORR

Anti-CD19 CAR NK cells

CD19

_

NCT05410041

I

Recruiting

To observe the safety and efficacy, and preliminarily evaluate the expansion of this product in vivo and the ORR after administration

Anti-CD19 CAR NK cells

CD19

CB-NK cells

NCT04796675

I

Recruiting

To evaluate the primary safety and efficacy

MDS

CAR.70/IL-15 transduced CB-NK cells

CD70

CB-NK cells

NCT05092451

I/II

Recruiting

To determine the safety, efficacy and optimal cell dose

NKX101

NKG2DL

Allogeneic NK cells

NCT04623944

I

Recruiting

To determine safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response

MM

FT576

BCMA

Allogenic NK cells

NCT05182073

I

Recruiting

Dose-escalation study. Till July 2022, no dose-limiting toxicities and no events of any grade of CRS, immune effector cell-associated neurotoxicity syndrome or GvHD were observed among the 9 evaluable patients

Anti-BCMA CAR NK cells

BCMA

Umbilical or CB-NK cells

NCT05008536

Early I

Recruiting

To assess the safety and feasibility

Anti-BCMA CAR NK92 cells

BCMA

NK92 cells

NCT03940833

I/II

Unknown status

To assess the safety and feasibility

Anti-BCMA CAR NK cells

BCMA

_

NCT05652530

Early I

Recruiting

To evaluate the safety and tolerability, and determine the MTD

B Cell Lymphoma

Anti-CD19 CAR NK cells

CD19

CB-NK cells

NCT05472558

I

Recruiting

To assess the safety and efficacy

CD19

_

NCT05410041

I

Recruiting

To observe the safety and efficacy, and preliminarily evaluate the expansion of this product in vivo and the ORR after administration

CD19

CB-NK cells

NCT04796675

I

Recruiting

To evaluate the safety and efficacy

CD19

HLA haploidentical NK cells

NCT04887012

I

Recruiting

To study the safety and efficacy

CD19

_

NCT04639739

Early I

Not yet recruiting

To manifest the safety and efficacy

CD19

_

NCT03690310

Early I

Unknown status

To manifest the safety and efficacy

CD19

_

NCT05570188

I/II

Recruiting

The administration time was 1–7 days after hematopoietic stem cell infusion, to evaluate long-term efficacy and safety

CD19

_

NCT05645601

I

Recruiting

To investigate the safety and efficacy of JD010 (CAR-NK product)

CD19

_

NCT05654038

I/II

Recruiting

To evaluate the efficacy and safety

CD19

_

NCT05673447

Early I

Not yet recruiting

To determine the safety and effectiveness

FT596

CD19

iPSC-derived NK cells

NCT04245722

I

Terminated

Till 25 June 2021, no dose-limiting toxicities or GvHD were reported. The ORR of whole cohort was 52.9%

CNTY-101

CD19

Induced pluripotent stem cells

NCT05336409

I

Not yet recruiting

To evaluate the safety, PK, and preliminary efficacy

CAR.5/IL15-transduced CB-NK cells

CD5

CB-NK cells

NCT05110742

I/II

Not yet recruiting

To determine the safety, efficacy and optimal cell dose

CAR.70/IL-15 transduced CB-NK cells

CD70

CB-NK cells

NCT05092451

I/II

Recruiting

To determine the safety, efficacy and optimal cell dose

NKX019

CD19

Allogeneic NK cells

NCT05020678

I

Recruiting

To evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response

CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells

CD19

CD28

CB-NK cells

NCT03056339

I/II

Active, not recruiting

To determine the safety and relative efficacy, assess the ORR

Anti-CD22 CAR NK Cells

CD22

_

NCT03692767

Early I

Unknown status

To investigate the safety and efficacy

Anti-CD19/CD22 CAR NK Cells

CD19

CD22

_

NCT03824964

Early I

Unknown status

To investigate the safety and efficacy

CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells

CD19

CD28

Umbilical or CB-NK cells

NCT03579927

I/II

Withdrawn

To establish the safety and relative efficacy

T Cell Lymphoma

CAR.5/IL15-transduced CB-NK cells

CD5

CB-NK cells

NCT05110742

I/II

Not yet recruiting

To determine the safety, efficacy and optimal cell dose

Anti-CD7 CAR NK cells

CD7

Induced pluripotent stem cells

NCT02742727

I/II

Recruiting

To evaluate the safety and efficacy