PXD042914

PXD042914 is an original dataset announced via ProteomeXchange.

Title	Dimeric IgA specifically disables intracellular mutated oncodrivers
Description	Despite their long half-life, therapeutic antibodies are considered ineffective against intracellular antigens due to their perceived inability to penetrate epithelial cells. Using recombinant antibodies targeting common mutations in oncogenes, we show that dimeric IgA, but not the same antibody on an IgG backbone, penetrates human epithelial cancer cells through PIGR-dependent directional transcytosis, specifically neutralizing mutated oncodrivers and expelling antigens outside the cell, bound to secretory IgA. Accordingly, targeting of KRasG12D or IDH1R132H with antigen-specific dimeric IgA abrogated the growth of different carcinomas in a mutation-specific manner, including in syngeneic tumor-bearing immunocompetent mice. Our results provide a rationale for developing PIGR-targeting tumor cell-penetrating antibodies to effectively target common mutations in intracellular oncogenes that drive many aggressive and frequent human cancers.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:35:19.807.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-12 08:36:26	ID requested
⏵ 1	2025-05-06 09:35:20	announced

10.1016/j.immuni.2023.09.013;

Biswas S, Mandal G, Anadon CM, Chaurio RA, Lopez-Bailon LU, Nagy MZ, Mine JA, H, ä, nggi K, Sprenger KB, Innamarato P, Harro CM, Powers JJ, Johnson J, Fang B, Eysha M, Nan X, Li R, Perez BA, Curiel TJ, Yu X, Rodriguez PC, Conejo-Garcia JR, Targeting intracellular oncoproteins with dimeric IgA promotes expulsion from the cytoplasm and immune-mediated control of epithelial cancers. Immunity, 56(11):2570-2583.e6(2023) [pubmed]

submitter keyword: transcytosis, cancer, therapeutic antibodies,Immunoglobulin A

José Conejo-Garcia
contact affiliation	Department of Integrated Immunobiology Duke School of Medicine Durham, NC, USA
contact email	jose.conejo-garcia@duke.edu
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
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/2025/05/PXD042914

PRIDE project URI

• PRIDE
  1. PXD042914
     1. Label: PRIDE project
     2. Name: Dimeric IgA specifically disables intracellular mutated oncodrivers