Table 3.
Preclinical and clinical studies of CAR-T and CAR-NK cells for acute myeloid leukemia at the 2022 ASH annual meeting.
| Author (REF) | Albinger [166] | Ehninger [167] | Sallman [168] | Naik [169] | Kloos [170] | Sallman [161] |
|---|---|---|---|---|---|---|
| Study type | Preclinical | Clinical (phase I, dose-escalation) | Clinical (phase I, dose-escalation) | Clinical | Preclinical | Clinical |
| Target | CD33 | CD123 | CD123 | CD123 | CD7/CD33 | CD33 |
| Cell source | NK | UniCAR-T | Anti. CD123 allogeneic CAR-T | CAR-T | CAR-T | Ultra CAR-T |
| Disease | AML | R/R AML, CD123+ | R/R AML, CD123+ | R/R pediatric AML, CD123+ | AML cells | R/RAMLs and MDSs |
| Innovation | NKG2A-KO | CD28 costimulatory domain | TRAC and CD52 gene disruption to minimize GVHD | Bridge to allo-HCT | Double target on leukemia cells | Membrane-bound Il-15 |
| Setting | In vitro and in vivo (mice) | In vivo (14 patients) | In vivo (16 patients) | In vivo (12 patients) | In vivo (mice) | In vivo (24 patients) |
| Results | In vitro AML increased cytotoxicity In vivo AML cells and leukemia-initiating cell elimination |
Good safety and tolerability CRS grade 1–2 (12 patients), CRES (1 patient), blast count reduction (10 patients), CRi (2 patients), flow cytometric MRD negativity (1 patient) |
Good safety and tolerability CRS 15/16 (≥3 3 patients) Evidence of UCART123 activity 4/16 SD, 2 patients; blast cell reduction, 1 patient; MRD-negative CR, 1 patient) |
Good safety and tolerability No grade 2 CRS or CRES No response (2 patients); reduction in blast cells (1 patient); CR (1 patient) |
Depletion of AML cells to 2.6–2.9% Prolonged survival |
Good safety and tolerability Grade 3 CRS (1 patient) Dose-dependent expansion of Ultra CAR-T; durable persistence 30% ORR: 1 CRi; 1 CRh; 1 PR No response in MDSs |
NKG2A: natural killer group 2A; KO: knockout; TRAC: T-cell receptor alpha constant; GVHD: graft versus host disease; SD: stable disease; MRD: minimal residual disease; CR: complete remission; CRi: complete remission with incomplete hematologic recovery; CRS: cytokine-release syndrome; CRES: CAR-T related encephalopathy syndrome; allo-HCT: allogeneic hematopoietic cells transplantation; PR: partial response.