PXD023034

PXD023034 is an original dataset announced via ProteomeXchange.

Title	An Unbiased Strategy for Selecting Effective Combinations of Therapeutic Targets Supports the Development of a Novel Bispecific Antibody with Tumor-Suppressing Properties
Description	Recent progress in dissecting molecular mechanisms essential for the survival and propagation of cancer cells triggered rapid development of targeted therapies. Although many of these therapies produce impressive initial responses in tumor suppression, the onset of resistance is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the development of effective combination therapies. Unfortunately, selection of optimal targets for combinatorial treatments is often confounded by limitations in our understanding of tumor biology. Here, we describe an unbiased comprehensive strategy that combines ex-vivo shRNA-based genome wide screening, proteomic profiling using BioID and patient tumor sequencing data analyses to overcome current challenges in identifying the best fit co-targeting agents. Integrating these strategies, we selected EGFR and EPHA2 receptors as molecules of choice for co-targeting in cancer cells, and generated a bispecific fully humanized anti-EGFR/EPHA2 antibody with druggable bioanalytical properties that very effectively suppresses tumor growth compared to its prototype therapeutic anti-EGFR antibody, cetuximab. Despite the overactivation of EGFR signaling in multiple malignancies, the therapeutic applicability of cetuximab is limited due to frequent resistance and could benefit from being used in a combination with another targeted compound. Our analysis indicates that EGFR and EPHA2 expression positively correlate in various cancer types and thus, are available for co-targeting in most tumors. Therefore, our work not only presents an efficient unbiased strategy for selecting optimal targets for combination therapies, but also describes a novel bispecific antibody, which has a high potential for being developed into a new clinically-relevant biologics effective in a broad variety of malignancies.
HostingRepository	PRIDE
AnnounceDate	2023-01-27
AnnouncementXML	Submission_2023-01-27_07:49:29.825.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023034
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sara LuizaBanerjee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-10 00:05:52	ID requested
⏵ 1	2023-01-27 07:49:30	announced

10.6019/PXD023034;

submitter keyword: Bispecific anti-EGFR/EPHA2 antibody

EPHA2 receptor

BioID

proximity proteomics

NicolasBisson
contact affiliation	Centre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Québec, QC, Canada Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, Canada Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC, Canada
contact email	Nick.Bisson@crchudequebec.ulaval.ca
lab head
Sara LuizaBanerjee
contact affiliation	Institut de recherches cliniques de Montréal - McGill University
contact email	banerjee.sara@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/01/PXD023034

PRIDE project URI

• PRIDE
  1. PXD023034
     1. Label: PRIDE project
     2. Name: An Unbiased Strategy for Selecting Effective Combinations of Therapeutic Targets Supports the Development of a Novel Bispecific Antibody with Tumor-Suppressing Properties