Table 5 Selected preclinical and clinical studies of CAR‐T and CAR-NK cell therapy for acute myeloid leukemia at the 2021 ASH annual meeting

Study type

Preclinical

Clinical

Clinical

Preclinical

Preclinical

Preclinical

Preclinical

Target

Preferentially Expressed Antigen in Melanoma (PRAME)

MICA/Micb

CD33

CD33

CD70

FLT3 and/or CD33

CLL-1

Cell source

T cells

T cells

T cells

T cells

Human peripheral blood NK cells

Allogeneic NK cells

Healthy donor peripheral blood NK cells

Disease

AML

AML/MDS

AML/MDS

AML

CD70 positive hematological and solid malignancies

AML

AML

Innovation

Target intracellular antigens by TCR mimic (mTCR) antibodies

Co-expression of shRNA with the NKG2D CAR

PRGN-3006 UltraCAR-T: non-viral gene delivery to simultaneously express CD33 CAR, membrane bound IL-15 (mbIL15) and kill switch; < 48 h without ex vivo expansion

Pharmacologically controlled by low dose of rapamycin

Non-viral TcBuster™ Transposon System; knockout of CD70 by CRISPR/Cas9 editing;

OR and NOT logic gated CAR gene circuit

Tc Buster (TcB) transposon system carrying a second generation CLL-1 CAR (CD28/CD3ζ or 41BB/CD3ζ) and hyperactive TcB transposase mRNA

Setting

In-vitro and in-vivo (mice)

Phase 1 first-in-human CYCLE-1 trial (NCT04167696)

Phase 1/1b first-in-human clinical trial (NCT03927261)

in-vitro and in-vivo (mice)

In vitro

In vitro

In vitro

Results

Anti-tumor reactivity of PRAME mTCR CAR-T cells can be enhanced by IFN-γ

7/11 patients: stable disease; good safety and tolerability

ORR 50% at dose level 1–3 × 10⁵/kg; good safety and tolerability

A phase 1 trial clinical trial is ongoing

Enhanced persistence of CAR-NK cells;

resistant to fratricide

OR gate: increase AML tumor clearance to prevent relapse;

NOT gate: protect healthy HSCs from off-tumor toxicity

Enhanced in vivo persistence and improved metabolic health by knocking out CISH gene using CRISPR/Cas9 editing