Table 4.

Clinical trials of CAR T-cells, NK Cells, and vaccine-based therapies for MDS and AML.

Study	Trial Identification	Mechanism	Study Population	Study Status	Results	MRD Status	Adverse Effects	Ref
CAR T-Cells
Phase 1 dose-escalation trial	NCT02203825	NKG2D CAR T-Cells	AML, MDS, or R/R MM without prior lymphodepleting conditioning	Completed	Robust efficacy not observed; response % not reported	N/A	No adverse events related to NKG2D CAR-T cells	[128]
NK Cells
Phase 1/2 adoptive immunotherapy trial	EudraCT number 2011-003181-32	IL-2 activated haploidentical NK cells	R/R high-risk myeloid malignancies	Completed	Objective response: 6/16 (38%) in patients with MDS and AML	N/A	Transient, treatable grade 3–4 toxicities including chills and nausea in 2/6 patients	[129]
Vaccine-based therapy
Phase 1 dose-escalation trial	UMIN000011519.	WT1-specific TCR-T cell transfer	R/R AML and high-risk MDS expressing WT1 antigen	Completed	WT1 specific TCR T-cells survived in AML and MDS and displayed reactivity to WT1; hematologic efficacy was not established.	N/A	No dose-limiting toxicities	[130]
Single-center, phase 1 study	NCT01834248	NY-ESO-1 vaccine administered with standard dose decitabine induced NY-ESO-1 expression in circulating blasts.	MDS or low blast count AML	Completed	7 patients reached the end of the study, 7/7 (100%) demonstrated induction of NY-ESO-1 expression, 6/7 patients (86%) and 4/7 patients (57%) demonstrated NY-ESO-1 specific CD4+ and CD8+ T-lymphocyte response	N/A	Related to decitabine: cytopenias, elevated liver enzymes, fatigue, edema, diarrhea. Majority of patients developed localized skin reaction to the vaccine.	[131]

Abbreviations: CAR-T-cell, chimeric antigen receptor T-cell; NK cell, natural killer cell; MDS, myelodysplastic syndrome; AML, acute myeloid leukemia; MRD, measurable residual disease; RR M/M, relapsed/refractory multiple myeloma.