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Enhancing the anti-tumor efficacy of Bispecific T cell engagers via cell surface glycocalyx editing

ABSTRACT: Enhancing the anti-tumor efficacy of Bispecific T cell engagers via cell surface glycocalyx editing

PROVIDER: PRJNA1030938 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26463750_1.fastq.gz	Fastqsanger.gz
	SRR26463750_2.fastq.gz	Fastqsanger.gz
	SRR26463751_1.fastq.gz	Fastqsanger.gz
	SRR26463751_2.fastq.gz	Fastqsanger.gz
	SRR26463752_1.fastq.gz	Fastqsanger.gz

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Enhancing the anti-tumor efficacy of Bispecific T cell engagers via cell surface glycocalyx editing

Project description:Bispecific T-cell engager (BiTE)-based cancer therapies that activate the cytotoxic T cells of a patient’s own immune system have gained momentum with the recent FDA approval of Blinatumomab for treating B cell malignancies. However, this approach has had limited success in targeting solid tumors. We have reported the development of BiTE-sialidase fusion proteins that enhance tumor cell susceptibility to BiTE-mediated cytolysis by T cells via targeted desialylation at the BiTE-induced T cell-tumor cell interface. Targeted desialylation results in better immunological synapse formation, T-cell activation and effector function. As a result, BiTE-sialidase fusion proteins show remarkably increased efficacy in inducing T-cell-dependent tumor cell cytolysis in response to target antigens compared to the parent BiTE molecules alone. This enhanced function is seen both in vitro and in in vivo xenograft and syngeneic solid tumor mouse models. Our findings highlight BiTE-sialidase fusion proteins as promising candidates for the development of next-generation bispecific T-cell engaging molecules for cancer immunotherapy. This transcriptomic dataset documents the effect of BiTE-sialidase vs uncojugated BiTE on T cells including the upregulation of effector associated genes.

2024-06-05 | GSE245991 | GEO

DNA hypomethylating agents potentiate the efficacy of CD3 bispecific T cell engagers [BiSulfite-seq]

Project description:Bispecific T cell engagers targeting tumor-associated antigens and CD3 are promising novel targeted therapeutic agents for both solid and hematologic cancers. However, prolonged TCR stimulation can lead to chromatin rewiring and T cell dysfunction. Here, we investigate the combination of bispecific T cell engagers with the DNA hypomethylating agent decitabine and observe suppressed tumor growth in preclinical models. Utilizing the PSMAxCD3 bispecific antibody for the treatment of prostate carcinoma and in vivo humanized models, we catalog, at the single-cell level, the dynamics of T cell epigenetic states during bispecific therapy, and in combination with decitabine. Importantly, this combination preserves a progenitor exhausted T cell population and delays acquisition of a dysfunctional state, at both chromatin and protein levels. At the DNA methylation level, TCR stimulation in the presence of decitabine maintains a naive-like pattern in gene loci associated with T cell stemness. This study provides a rich resource for understanding the evolution of T cell states during immunotherapy and mechanistic support for combining epigenetic modifiers with bispecific T cell engagers in the clinic.

2026-06-01 | GSE310428 | GEO

DNA hypomethylating agents potentiate the efficacy of CD3 bispecific T cell engagers [scATAC-seq]

2026-06-01 | GSE310545 | GEO

DNA hypomethylating agents potentiate the efficacy of CD3 bispecific T cell engagers [BiSulfite-seq]

Project description:DNA hypomethylating agents potentiate the efficacy of CD3 bispecific T cell engagers [BiSulfite-seq]

| PRJNA1365923 | ENA

DNA hypomethylating agents potentiate the efficacy of CD3 bispecific T cell engagers [scATAC-seq]

Project description:DNA hypomethylating agents potentiate the efficacy of CD3 bispecific T cell engagers [scATAC-seq]

| PRJNA1366492 | ENA

Single-cell mapping of the glycocalyx in the adult human and mouse ocular surface

Project description:The glycocalyx is a critical but often underappreciated modulator of cellular behavior. Its diversity across cell types within tissues remains poorly understood, but recent advances in single-cell profiling now enable more precise analysis of cell surface composition. Here, we applied single-cell glycan and RNA sequencing to profile glycocalyx diversity across human and mouse ocular surface cell types. Glycocalyx patterns effectively distinguished epithelial subtypes, with corneal epithelial cells enriched in complex and high-mannose N-glycans, conjunctival cells in fucosylated structures, and goblet cells in O-glycans. We also observed dynamic changes during epithelial maturation, marked by regulated shifts in sialic acid structures. In the mouse ocular surface, glycocalyx patterns distinguished major cell types, but the glycan profiles differed from those in humans, pointing to species-specific features. These findings demonstrate that glycocalyx composition is closely linked to cell identity and maturation and provide a foundation for exploring its roles in tissue organization and disease.

2025-11-18 | GSE299152 | GEO

Immunostimulatory CELMoD combination overcomes resistance to T cell engagers caused by high multiple myeloma burden

Project description:Bispecific T cell engagers (TCE) targeting BCMA and CD3 induce deep hematologic responses in approximately 60% of heavily pre-treated multiple myeloma (MM) patients. Pre-treatment with iberdomide and dexamethasone reshaped the bone marrow T cell compartment, promoted infiltration of naïve T cells, and generated 100% response rates and the longest survival in subjects with high tumor burden. This was accompanied by more favorable T cell profiling, with limited expansion of regulatory T cells and exhaustion. In total, administering TCE following dexamethasone and iberdomide treatments provided deeper and more durable responses with reduced risk of CRS. Whole Bone Marrow single cell profiling of immune phenotype of untreated and treated de novo Vk murine model.

2025-08-01 | GSE302797 | GEO

Enhancing the iNKT cell immunotherapy platform by combining optimised CAR endodomains with novel iNKT engagers

Project description:Enhancing the iNKT cell immunotherapy platform by combining optimised CAR endodomains with novel iNKT engagers

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Glycocalyx micro- and nanodomains in cell-cell and cell-matrix adhesions revealed by sensitive click chemistry

Project description:The glycocalyx consists of glycoproteins, glycolipids and extracellular polysaccharides at the cell surface which mediate viscoelastic and electrostatic barrier function. In molecular interactions the glycocalyx is thought to segregate locally to facilitate receptor-ligand binding, yet high-resolution maps of glycocalyx domains in cell-cell and cell-matrix interactions are lacking. We here applied TMTH-sulfoximine (THS)-based biorthogonal chemistry in live-cell culture and demonstrate much-enhanced glycocalyx detection, compared to established dibenzocyclooctyne-based labeling. Using superresolution microscopy, we identified micron-scale moderately diminished glycocalyx in cell-cell contacts and subtotal depletion in protrusions at the leading and trailing edges and membrane blebs when cells invaded 3D fibrillar matrix. At contacts to collagen fibrils, focal integrin clusters segregated in outward-protrusive nanodomains from glycocalyx (distance: 350 nm), forming adhesion sites of low glycocalyx content. Thus, THS-based next-generation bioorthogonal labelling of live cells identifies micro- and nanodomains with altered glycocalyx density, implicating local glycocalyx downregulation in functional cell-cell and cell-matrix interactions.

2025-03-18 | GSE287160 | GEO

The Preexisting T Cell Landscape Determines Response to T Cell-Engagers Therapy

Project description:Adaptive immunotherapy including bispecific T cell engagers (TCE) has shown promise in the treatment of various cancers, but clinical responses are heterogeneous and often not durable. As response to TCE is suggested to be independent of tumor recognition and T cell state, molecular determinants or mediators of primary and acquired resistance towards TCE remain poorly understood. Here, we identify conserved behaviors of bone marrow residing CD4+ and CD8+ T cells in multiple myeloma patients undergoing TCE therapy. We show that the bone marrow immune landscape reacts to TCE therapy with cell state-dependent clonal T cell expansion and herewith infer coupling of tumor recognition via MHC-I, T cell exhaustion and clinical response. While we find the abundance of exhausted-like memory CD8+ T cell clones to be associated with clinical response failure, we describe loss of target epitope and MHC class I expression as tumor-intrinsic mechanisms of acquired resistance to TCE.

2023-03-09 | GSE217245 | GEO

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