Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell mRNA sequencing of anti-PD-1 GITR-L bispecific antibody treated CT26 mouse tumor model infiltrating leukocytes

ABSTRACT: Single-cell mRNA sequencing of anti-PD-1 GITR-L bispecific antibody treated CT26 mouse tumor model infiltrating leukocytes

PROVIDER: PRJNA785871 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Single-cell mRNA sequencing of anti-PD-1 GITR-L bispecific antibody treated CT26 mouse tumor model infiltrating leukocytes

Project description:Single-cell mRNA sequencing of anti-PD-1 GITR-L bispecific antibody treated CT26 mouse tumor model infiltrating leukocytes

2021-12-20 | GSE190105 | GEO

Gene expression based outcome of CT-26 tumor in C57/BL6 mice after treatment with anti-PD-1 antibody, GITR-L, combination or Bispecific molecules

Project description:Co-stimulatory receptors such as GITR play key roles in regulating the effector functions of T cells. Agonistic anti-GITR antibodies have been investigated as a cancer immunotherapy with demonstrated efficacy in pre-clinical models. In human clinical trials, however, GITR agonist antibodies have shown limited therapeutic effect which may be due to a suboptimal receptor clustering-mediated signaling. To overcome this potential limitation, a rational protein engineering approach is needed to optimize GITR agonist-based immunotherapies. Here we show a novel bispecific molecule consisting of an anti-PD-1 antibody fused with a multimeric GITR ligand (anti-PD-1-GITR-L) that induces a PD-1-dependent and FcγR-independent GITR clustering, resulting in an enhanced activation, proliferation, and memory differentiation of primed antigen-specific GITR+PD-1+ T cells. The anti-PD-1-GITR-L bispecific is a PD-1 directed GITR-L construct that has a different mechanism of action (MoA) than the co-administration of anti-PD-1 plus GITR-L and demonstrated a dose-dependent immunologically driven tumor growth inhibition in syngeneic, genetically engineered and xenograft humanized mouse tumor models. Combination of anti-PD-1-GITR-L with TGFβ inhibition or chemotherapy (gemcitabine), respectively, resulted in tumor remission in immunogenically cold and checkpoint blockade resistant mouse models. Dose-dependent correlations between target saturation and Ki67 and TIGIT up-regulation on memory T cells have been observed following a single dose of anti-PD-1-GITR-L bispecific in mice and non-human primates. Anti-PD-1-GITR-L thus represents a novel bispecific approach for directing GITR agonism for cancer immunotherapy.

2021-12-20 | GSE189359 | GEO

Changes in tumor infiltrating leukocytes following TA99 CAR T cell treatment

Project description:Tumor infiltrating leukocytes were analyzed by scRNAseq 9 days after treatment with TA99 (anti-TRP-1) CAR T cells with or without Super2 and IL-33 co-expression.

2022-03-29 | GSE199491 | GEO

Single cell gene expression analysis of mouse melanoma tumor infiltrating leukocytes

Project description:The tumor immune cell composition dictates cancer outcomes. To capture this tumor immune cell diversity, we isolated tumor infiltrating leukocytes from tamoxifen induced tumors of Tyr::CreER;BRAFCAPTENloxp mice for single cell RNA sequencing

2021-04-15 | GSE149615 | GEO

A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy

Project description:CD3-bispecific antibodies represent an important therapeutic strategy in oncology. These molecules work by redirecting cytotoxic T cells to antigen-bearing tumor cells. Although CD3-bispecific antibodies have been developed for several clinical indications, cases of cancer-derived resistance are an emerging limitation to the more generalized application of these molecules. Here, we devised whole-genome CRISPR screens to identify cancer resistance mechanisms to CD3-bispecific antibodies across multiple targets and cancer types. By validating the screen hits, we found that deficiency in IFNγ signaling has a prominent role in cancer resistance. Interestingly, IFNγ functions by stimulating the expression of T cell killing-related molecules in a cell type-specific manner. Additionally, by assessing resistance to the clinical CD3-bispecific antibody flotetuzumab, we identified core fucosylation as a novel and critical pathway to regulate flotetuzumab binding to the CD123 antigen. Disruption of this pathway resulted in significant resistance to flotetuzumab treatment. Moreover, proper fucosylation of CD123 is required for its normal biological functions. In order to treat the resistance associated with fucosylation loss, flotetuzumab in combination with an alternative targeting CD3-bispecific antibody demonstrated superior efficacy. Together, our study reveals multiple mechanisms that can be targeted to enhance the clinical potential of current and future T cell engaging CD3-bispecific antibody therapies.

2020-11-12 | GSE159547 | GEO

Transcriptome analysis of tumor infiltrating NK and T cells in CT26-bearing BALB/C mice

Project description:CT26 tumors were implanted subcutaneously into syngeneic BALB/C mice and allowed to grow for 15-25 days. Tumors were collected, mechanically dissociated, and immune cells enriched using Percoll gradient. Cells were then stained with viability dye, CD45, CD3, and NKp46 to FACS sort for T cells (Live/CD45+/CD3+/NKp46-) and NK cells (Live/CD45+/CD3-/NKp46+). Isolated tumor infiltrating NK and T cells were then processed for RNA sequencing analysis.

2020-06-01 | GSE145837 | GEO

Gene expression profiling of CD45+ leukocytes infiltrating the prostate of TRAMP and TRAMP-Jα18-/- (iNKT cell-deficient) mice

Project description:To investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.

2018-02-21 | GSE94359 | GEO

Tumour infiltrating leukocytes

Project description:Murine tumour infiltrating lymphocytes (CD8+ T cells) were index-sorted based on expression of CD8a and CD3e. Subsequently cDNA was generated from these samples using the Smart-seq2 protocol. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

2016-06-01 | E-ERAD-467 | biostudies-arrayexpress