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SUMOylation inhibition potentiates CAR T activity against Multiple Myeloma

ABSTRACT: SUMOylation inhibition potentiates CAR T activity against Multiple Myeloma

PROVIDER: PRJNA1136941 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR29837065_1.fastq.gz	Fastqsanger.gz
	SRR29837065_2.fastq.gz	Fastqsanger.gz
	SRR29837066_1.fastq.gz	Fastqsanger.gz
	SRR29837066_2.fastq.gz	Fastqsanger.gz

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SUMOylation inhibition potentiates CAR T activity against multiple myeloma (RNA-Seq)

Project description:SUMOylation inhibition potentiates CAR T activity against multiple myeloma (RNA-Seq)

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SUMOylation inhibition potentiates CAR T activity against Multiple Myeloma (scRNA-Seq)

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SUMOylation inhibition potentiates CAR T activity against multiple myeloma (RNA-Seq)

Project description:Chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against hematologic malignancies; however, tumor relapse occurs commonly due to T cell dysfunction presenting as exhaustion and loss of effector function. Here, we identified SUMOylation inhibition promoted T cell effector function and prevented T cell exhaustion. Combination of SUMO E1 inhibitor TAK-981, significantly potentiated CAR T cell anti-tumor activity and improved persistence of CAR-presenting T cells in vivo, presenting a potent novel therapeutic approach.

2024-07-18 | GSE272300 | GEO

SUMOylation inhibition potentiates CAR T activity against Multiple Myeloma (scRNA-Seq)

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SUMOylation inhibition potentiates CAR T activity against Multiple Myeloma

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-07-18 | GSE272475 | GEO

SUMOylation inhibition overcomes dexamethasone resistance in multiple myeloma

Project description:SUMOylation, a posttranslational modification, regulates proteins by covalent attachment of small ubiquitin-like modifier (SUMO) proteins to a lysine (Lys) residue on target proteins. Here we use TAK-981, a selective SUMO-activating enzyme (SAE) inhibitor, to inhibit global SUMOylation in glucocorticoid sensitive and resistant multiple myeloma cell lines.

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SUMOylation inhibition overcomes dexamethasone resistance in multiple myeloma

Project description:SUMOylation inhibition overcomes dexamethasone resistance in multiple myeloma

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CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy I

Project description:Multiple myeloma is characterized by frequent clinical relapses following conventional therapy. Recently, chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) has been established as a treatment for patients with relapsed or refractory disease. However, while >70% of patients initially respond to this treatment, clinical relapse and disease progression occurs in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune intrinsic mechanisms may contribute to this resistance. While there were no pre-existing T cell features associated with clinical outcomes, we found that patients with a durable response to CAR-T cell treatment had greater persistence of their CAR-T cells compared to patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR-T cells. These cells expand in vivo early after infusion but express exhaustion markers (HAVCR2 and TIGIT) and remain polyclonal. Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFβ. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.

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CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy II

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Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy

Project description:Despite the acknowledged effectiveness of BCMA chimeric antigen receptor T (CAR-T) cells in killing multiple myeloma (MM) cells, predicting treatment responsivity to BCMA CAR-T therapy remains a challenge. In this study, we demonstrated that the best overall responses (BORs) of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8+ effector T cell cytotoxic activity, and elevated type 1 conventional dendritic cell (cDC1) antigen presentation ability. Our study sheds light on MM microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.

2024-07-10 | GSE271915 | GEO

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