PXD071196

PXD071196 is an original dataset announced via ProteomeXchange.

Title	TCR T cells targeting IgA- and IgG-expressing multiple myeloma
Description	T-cell based therapies have shown remarkable efficacy in multiple myeloma (MM), yet the disease remains largely incurable. Here, we investigated the constant domains of the immunoglobulin heavy chain (IgH) as novel targets for therapeutic T-cell receptors (TCRs), after confirming high and homogeneous IGH expression in >95% of MM patients. MM cells secrete excessive monoclonal immunoglobulins (M-proteins) that drive complications but are inaccessible to CAR T-cell or antibody targeting. Peptides from IgA and IgG constant regions were eluted from HLA-A*02:01, and reactive TCRs were isolated from healthy donors using allo-HLA-A*02:01 presentation to circumvent self-tolerance. T cells engineered with two TCRs specific for IgA or IgG passed a stringent multi-tier safety screen and selectively eliminated MM cells from 20 HLA-A*02:01+ patients secreting the relevant IgH in vitro. In vivo, IgA-TCR T cells eradicated IgA+HLA-A*02:01+ MM cells in xenograft models and reduced circulating IgA in humanized PBMC mice. These findings establish immunoglobulin constant domains as viable TCR targets in MM, potentially making ~40% of patients of European descent eligible for TCR T cell therapy, and extension to additional HLA alleles could further broaden eligibility. The approach may also be applicable to lymphoma and antibody-mediated autoimmune diseases.
HostingRepository	PRIDE
AnnounceDate	2026-03-06
AnnouncementXML	Submission_2026-03-06_05:15:41.841.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	The Trung Tran
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-25 08:37:39	ID requested
⏵ 1	2026-03-06 05:15:42	announced

10.1182/BLOOD.2025031897;

submitter keyword: Humanized PBMC mice, Xenograft, IgG, Immunopeptidome, TCR, IgA, In vivo,Multiple myeloma (MM)

Johanna Olweus
contact affiliation	Professor, M.D., Ph.D. Head, Department of Cancer Immunology Institute for Cancer Research Oslo University Hospital Radiumhospitalet and PRIMA Center of Excellence, University of Oslo Oslo Norway
contact email	johanna.olweus@medisin.uio.no
lab head
The Trung Tran
contact affiliation	University of Oslo
contact email	thetrung1268@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/2026/03/PXD071196

PRIDE project URI

• PRIDE
  1. PXD071196
     1. Label: PRIDE project
     2. Name: TCR T cells targeting IgA- and IgG-expressing multiple myeloma