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ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [CITE-seq]

ABSTRACT: ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [CITE-seq]

PROVIDER: PRJNA1049459 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27118330.fastq.gz	Fastqsanger.gz
	SRR27118331.fastq.gz	Fastqsanger.gz
	SRR27118332.fastq.gz	Fastqsanger.gz
	SRR27118333.fastq.gz	Fastqsanger.gz
	SRR27118334.fastq.gz	Fastqsanger.gz

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ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [CITE-seq]

Project description:Glucocorticoids are key component of the immuno-chemotherapy regimens (e.g., R-CHOP, EPOCH-R, Hyper-CVAD) for the treatment of B-cell non-Hodgkin lymphoma (NHL). However, prolonged systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate (ADC) engineered to reduce glucocorticoid-associated toxicity while possessing three distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced Fc-mediated effector function via afucosylation of the antibody backbone. ABBV-319 elicited potent GRM-driven anti-tumor activity against multiple B-cell NHL cell lines in vitro as well as in cell line-derived xenografts (CDXs) and patient-derived xenografts (PDXs) in vivo. Remarkably, a single-dose of ABBV-319 induced sustained tumor regression and enhanced anti-tumor activity compared to repeat dosing of systemic prednisolone at the maximum tolerated dose (MTD) in mice. The unconjugated CD19 monoclonal antibody (mAb) also displayed anti-proliferative activity on a subset of B-cell lymphoma cell lines through the inhibition of PI3K signaling. Moreover, afucosylation of the CD19 mAb enhanced Fc-mediated antibody-dependent cellular cytotoxicity (ADCC), and this activity was maintained after conjugation with GRM payloads. Notably, ABBV-319 displayed superior efficacy compared to afucosylated CD19 mAb in human CD34+ PBMC-engrafted NSG-Tg(Hu-IL15) transgenic mice, demonstrating enhanced anti-tumor activity when different MOAs are combined. ABBV-319 also showed durable anti-tumor activity across multiple preclinical B-cell lymphoma models, including non-germinal center B-cell (GCB) DLBCL and relapsed lymphoma after R-CHOP treatment. Collectively, these data support the ongoing testing of ABBV-319 in Phase I clinical trial (NCT05512390)

2023-12-15 | GSE249542 | GEO

ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [RNA-seq]

2023-12-15 | GSE249023 | GEO

ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies

Project description:ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies

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ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [RNA-seq]

Project description:ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [RNA-seq]

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ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Project description:AbstractGlucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone. ABBV-319 elicited potent GRM-driven antitumor activity against multiple malignant B-cell lines in vitro, as well as in cell line-derived xenografts and patient-derived xenografts (PDXs) in vivo. Remarkably, a single dose of ABBV-319 induced sustained tumor regression and enhanced antitumor activity compared with repeated dosing of systemic prednisolone at the maximum tolerated dose in mice. The unconjugated CD19 monoclonal antibody (mAb) also displayed antiproliferative activity in a subset of B-cell lymphoma cell lines through the inhibition of phosphoinositide 3-kinase signaling. Moreover, afucosylation of CD19 mAb enhanced Fc-mediated antibody-dependent cellular cytotoxicity. Notably, ABBV-319 displayed superior efficacy compared with afucosylated CD19 mAb in human CD34+ peripheral blood mononuclear cell-engrafted NSG-Tg(Hu-IL15) transgenic mice, demonstrating enhanced antitumor activity when multiple MOAs are enabled. ABBV-319 also showed durable antitumor activity across multiple B-cell lymphoma PDX models, including nongerminal center B-cell diffuse large B-cell lymphoma and relapsed lymphoma after R-CHOP treatment. Collectively, these data support the ongoing evaluation of ABBV-319 in a phase 1 clinical trial.

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ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies

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

2023-12-15 | GSE249543 | GEO

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Brd2 inhibitor ABBV-744 inhibits SARS-CoV-2 infection in Syrian Hamsters

Project description:We tested if Brd2 inhibitor ABBV-744 could reduce SARS-CoV-2 infection in Syrian Hamsters. Three days post-infection, the lungs of hamsters were harvested and subjected to RNA-seq. Infected, but untreated, hamsters showed marked up-regulation of a number of genes including ISGs when compared to uninfected controls. In contrast, hamsters treated with ABBV-744 showed a down-regulation of ISG levels, confirming ABBV-744 activity. Thus, Brd2 inhibition can decrease SARS-CoV-2 infection in Syrian Hamsters.

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Identification of potential ABBV-075 responsive markers in mouse skin

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