Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumor-derived biomarkers beyond antigen expression enhance efficacy of CD276/B7H3 antibody-drug conjugate in metastatic prostate cancer

ABSTRACT: Tumor-derived biomarkers beyond antigen expression enhance efficacy of CD276/B7H3 antibody-drug conjugate in metastatic prostate cancer

PROVIDER: PRJNA992487 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Tumor-derived biomarkers beyond antigen expression enhance efficacy of CD276/B7H3 antibody-drug conjugate in metastatic prostate cancer

Project description:Antibody-drug conjugates(ADCs) are promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined for any cancer. We present a comprehensive therapeutic and biomarker analysis of a B7H3-ADC with pyrrolobenzodiazepine(PBD) payload in 26 treatment-resistant, metastatic prostate cancer(mPC) models. B7H3 is a tumor-specific surface protein widely expressed in mPC, and PBD is a DNA cross-linking agent. B7H3 expression was necessary but not sufficient for B7H3-PBD-ADC responsiveness. RB1 deficiency and/or replication stress, characteristics of poor prognosis, conferred sensitivity and were associated with complete tumor regression in both neuroendocrine (NEPC) and androgen receptor positive(ARPC) prostate cancer models, even with low B7H3 levels. Non-ARPC models, which are currently lacking efficacious treatment, demonstrated the highest replication stress and were most sensitive to treatment. In RB1 wild-type ARPC tumors, SLFN11 expression or select DNA repair mutations in SLFN11 non-expressors governed response. Significantly, wild-type TP53 predicted non-responsiveness (7/8 models). Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies.

2023-07-11 | GSE236808 | GEO

A Dual-Payload Antibody-Drug Conjugate Targeting CD276/B7-H3 Elicits Cytotoxicity and Immune Activation in Triple-Negative Breast Cancer

Project description:Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous disease that often relapses following treatment with standard radiotherapies and cytotoxic chemotherapies. Combination therapies have potential for treating refractory metastatic TNBC. Here, we aimed to develop an antibody-drug conjugate with dual payloads (DualADC) as a chemo-immunotherapy for TNBC. The overexpression of an immune checkpoint transmembrane CD276 (also known as B7-H3) was associated with angiogenesis, metastasis, and immune tolerance, in over 60% of TNBC patients. Development of a monoclonal antibody (mAb) capable of targeting the extracellular domain of surface CD276 enabled delivery of payloads to tumors, and a platform was established for concurrent conjugation of a traditional cytotoxic payload and an immunoregulating toll-like receptor 7/8 agonist to the CD276 mAb. The DualADC effectively killed multiple TNBC subtypes, significantly enhanced immune functions in the tumor microenvironment, and reduced tumor burden by up to 90-100% in animal studies. Single-cell RNA-sequencing, multiplex cytokine analysis, and histology elucidated the impact of treatment on tumor cells and the immune landscape. This study suggests that the developed DualADC could represent a promising targeted chemo-immunotherapy for TNBC.

2024-08-21 | GSE274871 | GEO

A Dual-Payload Antibody-Drug Conjugate Targeting CD276/B7-H3 Elicits Cytotoxicity and Immune Activation in Triple-Negative Breast Cancer

Project description:A Dual-Payload Antibody-Drug Conjugate Targeting CD276/B7-H3 Elicits Cytotoxicity and Immune Activation in Triple-Negative Breast Cancer

| PRJNA1148377 | ENA

RNA-seq analysis of CD276-high/EpCAM+ cells from HNSCC patient-derived-xenograft

Project description:We performed RNA sequencing (RNA-seq) to compare the gene expression pattern between CD276-high/EpCAM+ and CD276-low/EpCAM+ cells isolated from human HNSCC PDX. We identified a cohort of key oncogenes associate with cancer stemness enriched in CD276-high cells. Suggesting CD276 may play a positive role in maintaining cancer stem cells in human head and neck squamous cell carcinoma.

2021-05-28 | GSE132627 | GEO

Cd276

Project description:Rattus norvegicus Cd276, Cd276 molecule [Source:RGD Symbol;Acc:727815], is differentially expressed in 30 experiment(s);

| ENSRNOG00000033608 | ExpressionAtlas

Cd276

Project description:Rattus norvegicus Cd276, Cd276 molecule [Source:RGD Symbol;Acc:727815], is expressed in 5 baseline experiment(s);

| ENSRNOG00000033608 | ExpressionAtlas

CD276

Project description:Macaca mulatta CD276, CD276 molecule [Source:VGNC Symbol;Acc:VGNC:70826], is expressed in 3 baseline experiment(s);

| ENSMMUG00000005448 | ExpressionAtlas

CD276

Project description:Homo sapiens CD276, CD276 molecule [Source:HGNC Symbol;Acc:HGNC:19137], is differentially expressed in 142 experiment(s);

| ENSG00000103855 | ExpressionAtlas

CD276

Project description:Homo sapiens CD276, CD276 molecule [Source:HGNC Symbol;Acc:HGNC:19137], is expressed in 50 baseline experiment(s);

| ENSG00000103855 | ExpressionAtlas

CD276

Project description:Sus scrofa CD276, CD276 molecule [Source:VGNC Symbol;Acc:VGNC:86405], is differentially expressed in 2 experiment(s);

| ENSSSCG00000001917 | ExpressionAtlas

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