PXD042971

PXD042971 is an original dataset announced via ProteomeXchange.

Title	Highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer
Description	Discoidin domain-containing receptor 1 (DDR1) plays an important role in cancer progression. However, the DDR1 function in tumors is still elusive. We recently reported that DDR1 promoted collagen fiber alignment and formation of a physical barrier, which causes immune exclusion from tumors. We also demonstrated that our DDR1 ECD-targeting mAbs can disrupt collagen fiber alignment and increase T Cell infiltration in tumors. In this study, we humanized a DDR1 ECD-targeting mAb and showed significant antitumor efficacy in an immunocompetent mouse model. We determined the binding epitope using gene mutagenesis, hydrogen-deuterium exchange mass spectrometry (HDX-MS), and X-ray crystallography. Mechanistically, we showed that the humanized mAb inhibited DDR1 phosphorylation and, more importantly, blocked DDR1 shedding and disrupted a physical barrier formed by collagen fiber alignment in tumors. This study not only paves a pathway for development of PRTH-101 as a cancer therapeutic, but also broaden our understanding of the roles of DDR1 in modulation of collagen alignments in tumor extracellular matrix and tumor immune microenvironment.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:48:31.132.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jasmin Dülfer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-14 01:11:55	ID requested
1	2023-06-19 01:03:07	announced
2	2023-11-14 06:43:32	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:48:31	announced	2024-10-22: Updated project metadata.

10.1136/JITC-2023-006720;

submitter keyword: DDR1, breast cancer, PRTH-101, HDX-MS, mAb

Dr Zhiqiang An
contact affiliation	Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
contact email	Zhiqiang.An@uth.tmc.edu
lab head
Jasmin Dülfer
contact affiliation	Evotec SE
contact email	jasmin.duelfer@evotec.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/2023/06/PXD042971

PRIDE project URI

• PRIDE
  1. PXD042971
     1. Label: PRIDE project
     2. Name: Highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer