Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Humanized Monoclonal Antibody Targeting an Ectonucleotidase Rescues Heart Function after Myocardial Infarction

ABSTRACT: A Humanized Monoclonal Antibody Targeting an Ectonucleotidase Rescues Heart Function after Myocardial Infarction

PROVIDER: PRJNA1076596 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

A Humanized Monoclonal Antibody Targeting an Ectonucleotidase Rescues Heart Function after Myocardial Infarction

Project description:We have recently demonstrated that the ectonucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) is upregulated in the heart after myocardial infarction (MI) and initiates an aberrant metabolic cascade that worsens cell death and heart repair. Genetic loss of function approaches demonstrated that animals deficient in ENPP1 exhibited enhanced heart repair and had significantly superior post MI heart function. Whether human ENPP1 protein can be therapeutically targeted after heart injury remains unknown. Here, we engineer a humanized monoclonal antibody targeting human ENPP1 (hENPP1mAb) and demonstrate high affinity and specificity of binding to the catalytic domain of human ENPP1. In mice, genetically engineered, to express the human ENPP1 ortholog instead of murine ENPP1 (humanized ENPP1 mice), we demonstrate that administration of hENPP1mAb significantly rescued post MI heart function compared to IgG injected animals. Using metabolomics, single nuclear transcriptomics, and cellular respiration assays, we demonstrate that administration of the hENPP1mAb induces organ wide metabolic and transcriptional reprogramming of the heart that enhances myocyte cellular respiration and decreases cell death and fibrosis in the infarcted heart. Biodistribution and safety studies with radiolabeled hENPP1mAb showed specific organ wide distribution without any organ toxicity. Finally, in humanized ENPP1 animals that have also been genetically engineered to exhibit antibody clearance kinetics similar to humans, we demonstrate that a single "shot" of the hENPP1mAb after MI is sufficient to rescue post infarct cardiac dysfunction. Taken together our observations provide proof of concept on how the human ectonucleotidase ENPP1 can be therapeutically targeted to prevent heart failure after MI.

2024-10-14 | GSE255826 | GEO

Maytansinoid DM4-Conjugated Humanized Monoclonal Antibody huC242 in Treating Patients With Solid Tumors

Project description:RATIONALE: Monoclonal antibodies, such as maytansinoid DM4-conjugated humanized monoclonal antibody huC242, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase I trial is studying the side effects and best dose of maytansinoid DM4-conjugated humanized monoclonal antibody huC242 in treating patients with solid tumors that cannot be removed by surgery or have spread to other parts of the body.

| 2030868 | ecrin-mdr-crc

A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer

Project description:This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD) of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).

| 2190733 | ecrin-mdr-crc

myocardial infarction in Reg3beta knock-out mice

Project description:Affymetrix microarray analysis of molecular changes after myocardial infarction. Samples of heart tissue were analyzed after myocardial infarction from WT and reg3beta knock-out mice. Samples from scar tissue and samples adjacent to the scar were analyzed. In the experiment we primarily compared infarction zone of wild-type to infarction zone of knock-out animals, and remote zone of wild-type to remote zone of knock-outs.

2015-06-29 | E-MTAB-2561 | biostudies-arrayexpress

Spatial transcriptomics reveals distinct tumor microenvironment of murine breast cancer model undergoing treatment with a humanized monoclonal antibody targeting FABP4

Project description:Spatial transcriptomics reveals distinct tumor microenvironment of murine breast cancer model undergoing treatment with a humanized monoclonal antibody targeting FABP4

| PRJNA1100989 | ENA

MDS in Humanized Mice

Project description:MDS in Humanized Mice

| PRJNA517205 | ENA

MDS in Humanized Mice

Project description:MDS in Humanized Mice

| PRJNA517206 | ENA

CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers

Project description:This is a Phase 1/1b open-label, dose escalation and dose expansion study of CPI-006, a humanized monoclonal antibody (mAb) targeting the CD73 cell-surface ectonucleotidase in adult subjects with select advanced cancers. CPI-006 will be evaluated as a single agent, in combination with ciforadenant (an oral adenosine 2A receptor antagonist), in combination with pembrolizumab (an anti-PD1 antibody), and in combination with ciforadenant and pembrolizumab.

| 2267503 | ecrin-mdr-crc

Fasting Fed RNA sequencing experiment of mice with humanized livers

Project description:We report the RNA sequencing results of four fasting mice with humanized livers and four fed mice with humanized livers.

2019-10-04 | GSE126587 | GEO

Spatial transcriptomics reveals distinct tumor microenvironment of murine breast cancer model undergoing treatment with a humanized monoclonal antibody targeting FABP4

Project description:Circulating levels of adipocyte fatty acid binding protein (A-FABP, also known as FABP4) are linked with metabolic dysregulation. Our previous study demonstrated that high serum levels of FABP4 increased the risk of obesity associated breast cancer. The treatment with anti-FABP4 monoclonal anitbody was demonstrated to inhibit mammary tumor growth in a syngeneic mouse model. We hypothesized that spatial transcriptomic analysis would identidy the relationship between tumor cells and tumor-associated stromal cells during the antibody treatment.

2024-09-01 | GSE264099 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data