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Establishment of ganglioside GD2-expressing extranodal NK/T-cell lymphoma cell line with scRNA-seq analysis

ABSTRACT: Establishment of ganglioside GD2-expressing extranodal NK/T-cell lymphoma cell line with scRNA-seq analysis

PROVIDER: PRJNA1055061 | ENA |

REPOSITORIES: ENA

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Establishment of ganglioside GD2-expressing extranodal NK/T-cell lymphoma cell line with scRNA-seq analysis

Project description:Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL), known for its poor prognosis and association with Epstein-Barr virus, has a new development with the establishment of the ENKL-J1 cell line. Derived from a patient's bone marrow, ENKL-J1 cells express the ganglioside GD2, making them targets for GD2-directed chimeric antigen receptor T cells. This discovery positions GD2 as a potential therapeutic target. Genetic analysis of ENKL-J1 revealed variants in TP53 and TET2. Single-cell RNA sequencing indicated high expression of genes in key oncogenic pathways such as JAK-STAT, NF-κB, and MAPK, along with genes linked to multidrug resistance, tumor suppression, and anti-apoptosis. In vitro, molecular targeting agents like eprenetapopt, tazemetostat, and vorinostat effectively induced apoptosis in these cells, with GD2-directed T cells also showing cytotoxicity in vivo. The ENKL-J1 cell line, therefore, provides valuable insights for developing treatments for ENKL, especially in advanced stages.

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Ganglioside GD2 identifies Breast Cancer Stem Cells: Targeting GD3 Synthase Inhibits GD2 Expression and Tumor Growth

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies

Project description:Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies

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NGS based identification of GD2-positive tumor-specific phenotype for cancer diagnostics and therapy

Project description:The tumor-associated glycosphingolipid ganglioside GD2 presents an attractive target for cancer immunotherapy. This molecule is abundant on different types of cancer cells and is characterized by restricted expression on healthy cells. Tumors exhibit heterogeneity in the expression level of GD2 and, therefore, development of methods for determination of the GD2-positive tumor phenotype for the pertinent application of targeted therapies is required. In this work, we have developed a gene expression-based classifier for the prediction of the GD2-positive tumor phenotype. We analyze RNA-seq data from GD2-positive and GD2-negative cell lines of different tumor types as well as neuroblastoma biopsy material for gene expression levels of enzymes that participate in ganglioside biosynthesis and determine the role of gene expression of these enzymes in the formation of the GD2-positive tumor phenotype. We also apply gene expression patterns known from literature to our data and use large public RNA-seq datasets to identify novel gene expression patterns associated with GD2 expression to validate the findings in our data. The results of the study may be used for the development of a gene signature which separates GD2-positive from GD2-negative tumors and for prediction of the GD2 phenotype in clinical specimens from cancer patients, and thus be used as a companion diagnostic for anti-GD2 therapy.

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies IV

Project description:Purpose: This study uses a high-throughput glycan microarray to evaluate the immunological evolution of antibodies to the glyco-antigen GD2. The goal is to determine germline and affinity mature antibody specificity and affinities/ Results: Affinity mature anti-GD2 antibodies 3F8 and ch14.18 had high affinity and were highly specific for the target GD2. Germline antibodies were also hihgly specific and had surprisingly high affinity. Conclusion: Antibodies to GD2 evolved from highly specific germlines. Highly specific germlines may be critical in evading autoimmunity issues.

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies III

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies II

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