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Expression data from T-cell Acute Lymphoblastic Leukemia (T-ALL) patient-derived xenograft treated with anti-CD3 mAbs.

ABSTRACT: T-cell acute lymphoblastic leukemia is an aggressive hematological malignancy treated with chemotherapy and has a poor prognosis. In previous studies, we demonstrated that T cell receptor (TCR)-induced negative selection is highly effective in combating T-ALL in mouse models. Moreover, targeting the TCR of diagnostic T-ALL-derived PDX with anti-hCD3 (aCD3) mAb OKT3 or the clinically relevant aCD3 mAb Teplizumab resulted in leukemic cell death, regression of leukemia, and improved host survival. The objective of the present experiment is to uncover the molecular mechanisms responsible for the anti-leukemic properties of the anti-CD3 mAbs OKT3 and Teplizumab in a T-ALL PDX model. We compare the transcriptomic profiles of FACS-sorted T-ALL cells extracted from T-ALL patient-derived xenograft (PDX) treated for 6h with isotype control antibody IgG2a or OKT3 mAb or Teplizumab mAb.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240261 | GEO | 2024/03/19

REPOSITORIES: GEO

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Expression data from T-cell Acute Lymphoblastic Leukemia (T-ALL) patient-derived xenograft treated with anti-CD3 mAb

Project description:T-cell acute lymphoblastic leukemia is a hematological malignancy treated by chemotherapy, with a poor prognosis. We have demonstrated that activation of the T cell receptor (TCR) by anti-CD3 antibodies has a potent anti-leukemic effect in patient-derived xenograft models (PDX) of T-ALL. Therefore, with this experiment, we aim to identify the molecular mechanisms underlying the anti-leukemic properties of the OKT3 anti-CD3 mAb in T-ALL PDX.

2024-03-19 | GSE240296 | GEO

TCR repertoire analysis revealed the mobilization of novel CD8+ T cell clones into Cancer-Immunity Cycle following anti-CD4 antibody administration

Project description:Depletion of CD4+ cells by anti-CD4 monoclonal antibody (anti-CD4 mAb) induces expansion of tumor-reactive CD8+ T cells and exhibits strong antitumor effects in several murine tumor models. However, whether the anti-CD4 mAb treatment activates particular or a broad variety of tumor-reactive CD8+ T cell clones is not answered. To investigate the changes of TCR repertoire induced by the anti-CD4 mAb treatment, we performed unbiased high throughput TCR sequencing in a B16F10 mouse subcutaneous melanoma model.

2019-02-07 | GSE115425 | GEO

Identification of transcriptomic signatures for differentiation of CD4+ T cell subsets

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2022-12-20 | GSE210222 | GEO

Differential regulation patterns of anti-CD20 mAbs in MCL

Project description:We investigated the differential regulation patterns of type I anti-CD20 monoclonal antibody (mAb) rituximab and type II obinutuzumab on a transcriptional level. Using a panel of MCL cell lines, we determined the effects of obinutuzumab and rituximab as monotherapies as well as in combination on cell viability and proliferation. Obinutuzumab induced a higher reduction in cell proliferation in each mantle cell lymphoma cell line than rituximab did. Results indicate a common pattern of expression changes after binding of anti-CD20 mAbs, but also reveal a significant difference between type I and type II treatment. Combination treatment resulted in a rituximab-like expression pattern. Many deregulated genes were associated with stress signalling, cell death, immune response and other functional clusters. Our analyses identified different and antibody-specific downstream expression patterns of obinutuzumab and rituximab, which may represent the molecular basis of the superior effect of obinutuzumab in comparison to rituximab.

2014-12-31 | GSE54169 | GEO

Differential regulation patterns of anti-CD20 mAbs in MCL

2014-12-31 | GSE54169 | GEO

Blood-Tumor overlapping TCR repertoire predicts the clinical responses of PD-1 blockade in patients with gastrointestinal cancer[RNA-Seq]

Project description:As the anti-PD-1 monoclonal antibody (mAb) becomes to be used in many types of cancers, the needs for the predictive biomarker of PD-1 blockade are growing. T cell receptor (TCR) repertoire—which reflects the anti-tumor T-cell responses based on the antigen specificity—is a potential biomarker of cancer immunotherapy. Here, we analyzed the TCR repertoire of patients with advanced gastrointestinal cancer and explored its association with clinical responses.

2021-07-13 | GSE154538 | GEO

Blood-Tumor overlapping TCR repertoire predicts the clinical responses of PD-1 blockade in patients with gastrointestinal cancer [TCR-Seq]

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Microarray analysis of the migrating human CD4+ T cell population from the spleen of humanized mice in response to treatment with Teplizumab or hIg

Project description:In order to identify genes expressed by cells that leave the spleen, the spleens were harvested from untreated reconstituted humanized mice (N=4) and a single cell suspension was prepared . The cultures were treated with either teplizumab (anti human CD3 hOKT3g1(Ala-Ala)) or hIg for 18 hrs in vitro. Splenocytes were also harvested 18 hrs after reconstituted mice (N=4) were treated with teplizumab in vivo. The humanized mice used where NOD/SCID IL2gc-/- (NSG) reconstituted with human CD34+ at birth. Total RNA was obtained form sorted human CD4 splenocytes 18 hours post treatment. Comparsons were made between the treatment groups.

2012-02-27 | E-GEOD-34163 | biostudies-arrayexpress

Loss of B cell Tolerance is TCR Dependent [IgG2a CTD array]

Project description:We used protein arrays to measure IgG2a autoantibodies associated with Connective Tissue Diseases (CTDs) from retrogenic chimeras Sera was isolated from irradiated Icos-/-;CD45.1 mice reconstituted with 564Igi;Icos-/- bone marrow mixed with Icos-/-;CD45.1 bone marrow and WT bone marrow (BMchim.564) or retrogenic HSCs expressing TCR-A (BMchim.564-Icos.RAG-TCRA), TCR-B (BMchim.564-Icos.RAG-TCRB), or TCR-C (BMchim.564-Icos.RAG-TCRC). 564Igi (564homo) and 564Igi;Icos-/- (564homo.Icos) sera were included as controls.

2023-12-29 | GSE231801 | GEO

Transcription profiling by array of human T-ALL cells purified from the BM of mice treated with anti-Notch1 or control mAbs

Project description:We generated PDTALL19 xenograft by intravenously injection of primary T-ALL cells from BM of a newly diagnosed ALL pediatric patient in NOD/SCID mice. To test the effect of Notch1 blockade on PDTALL19 cells engraftment, mice were treated with anti-human Notch1 mAb OMP-52M51 (OncoMed Pharmaceuticals Inc., Redwood, CA) or control antibody (Rituximab, Roche, Basel, Switzerland) (6 mice/group). Three independent experiments (1, 2, 3) were performed. In each experiment T-ALL cells from the BM of different mice were pooled, sorted and finally RNA was extracted. Differential expression analysis identified 194 up- and 209 down-regulated genes (BH-FDR<0.05 and absolute FC>1.5) in anti-Notch1 vs. control Ab treated samples.

2013-11-15 | E-MTAB-1349 | biostudies-arrayexpress

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