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Allogeneic HSPC-engineered CD33-targeting CAR-NKT cells synergize with hypomethylating agents for effective and safe treatment of myeloid malignancies

ABSTRACT: Allogeneic HSPC-engineered CD33-targeting CAR-NKT cells synergize with hypomethylating agents for effective and safe treatment of myeloid malignancies

PROVIDER: PRJNA1126626 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29487833_1.fastq.gz	Fastqsanger.gz
	SRR29487833_2.fastq.gz	Fastqsanger.gz
	SRR29487834_1.fastq.gz	Fastqsanger.gz
	SRR29487834_2.fastq.gz	Fastqsanger.gz
	SRR29487835_1.fastq.gz	Fastqsanger.gz

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Allogeneic HSPC-engineered CD33-targeting CAR-NKT cells synergize with hypomethylating agents for effective and safe treatment of myeloid malignancies

Project description:Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for targeting myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, autologous approaches pose significant challenges in manufacturing and patient selection, emphasizing the need for off-the-shelf cell products. In this study, we systematically characterized primary AML and MDS patient samples, identifying a unique therapeutic opportunity for CAR-engineered invariant natural killer T (CAR-NKT) cell therapy. Utilizing a clinically guided culture method, we generated allogeneic IL-15-enhanced CD33-targeting CAR-NKT (Allo15CAR33-NKT) cells through HSPC engineering and an ex vivo, feeder-free HSPC differentiation culture. These cells demonstrated potent antitumor efficacy against blast cells via multiple tumor-targeting mechanisms. In vivo, Allo15CAR33-NKT cells exhibited effective tumor homing, expansion, and persistence, characterized by high effector function and low exhaustion propensity. Furthermore, these cells synergized with hypomethylating agent (HMA) treatment, which upregulated CD1d and NK ligand expression on tumor cells, enhancing susceptibility to Allo15CAR33-NKT cell-mediated killing. Notably, Allo15CAR33-NKT cells displayed minimal off-tumor effects against hematopoietic precursors, and low risks of graft-versus-host disease and cytokine release syndrome, highlighting their substantial therapeutic potential for myeloid malignancies.

2025-01-01 | GSE270430 | GEO

Cd33

Project description:Rattus norvegicus Cd33, CD33 molecule [Source:RGD Symbol;Acc:1596020], is differentially expressed in 23 experiment(s);

| ENSRNOG00000037331 | ExpressionAtlas

Cd33

Project description:Rattus norvegicus Cd33, CD33 molecule [Source:RGD Symbol;Acc:1596020], is expressed in 5 baseline experiment(s);

| ENSRNOG00000037331 | ExpressionAtlas

CD33

Project description:Macaca mulatta CD33, CD33 molecule [Source:VGNC Symbol;Acc:VGNC:81368], is expressed in 3 baseline experiment(s);

| ENSMMUG00000009486 | ExpressionAtlas

CD33

Project description:Homo sapiens CD33, CD33 molecule [Source:HGNC Symbol;Acc:HGNC:1659], is differentially expressed in 124 experiment(s);

| ENSG00000105383 | ExpressionAtlas

CD33

Project description:Homo sapiens CD33, CD33 molecule [Source:HGNC Symbol;Acc:HGNC:1659], is expressed in 29 baseline experiment(s);

| ENSG00000105383 | ExpressionAtlas

Cd33

Project description:Mus musculus Cd33, CD33 antigen [Source:MGI Symbol;Acc:MGI:99440], is differentially expressed in 112 experiment(s);

| ENSMUSG00000004609 | ExpressionAtlas

CD33

Project description:Papio anubis CD33, CD33 molecule [Source:HGNC Symbol;Acc:HGNC:1659], is expressed in 1 baseline experiment(s);

| ENSPANG00000015649 | ExpressionAtlas

Cd33

Project description:Mus musculus Cd33, CD33 antigen [Source:MGI Symbol;Acc:MGI:99440], is expressed in 27 baseline experiment(s);

| ENSMUSG00000004609 | ExpressionAtlas

CD33

Project description:Chlorocebus sabaeus CD33, CD33 molecule [Source:HGNC Symbol;Acc:HGNC:1659], is expressed in 1 baseline experiment(s);

| ENSCSAG00000002037 | ExpressionAtlas

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