PXD060726

PXD060726 is an original dataset announced via ProteomeXchange.

Title	TIMEPOINT, a phase 1 study of MTL-CEBPA in combination with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumours.
Description	Many cancer patients don’t benefit from currently-approved immune checkpoint inhibitors (ICI), suggesting that additional immunomodulation of the immunosuppressive tumour microenvironment (TME) is required. MTL-CEBPA specifically upregulates expression of master myeloid transcription factor, CEBPA, relieving myeloid-driven immunosuppression. Here, we report the safety, tolerability, pharmacokinetics, and efficacy of MTL-CEBPA in combination with pembrolizumab in patients with advanced solid tumours that typically show ICI resistance. Multimodal exploratory analyses of paired patient biopsies demonstrate biological changes associated with combination treatment of MTL-CEBPA and pembrolizumab, including increased infiltration of T cell and antigen-presenting cells supporting conversion from an immune desert towards a more immune-inflamed TME. Patients with disease stabilisation demonstrate reductions in immunosuppressive myeloid cells post-treatment. Collectively, these data support a role for MTL-CEBPA in reducing immunosuppression in the TME. This study was registered at ClinicalTrials.gov (NCT04105335). This manuscript also reports proteomic data from patients treated with MTL-CEBPA in combination with sorafenib from clinical trial, OUTREACH, accessible at ClinicalTrials.gov, number NCT02716012 and reported. Stored plasma from patients from this clinical trial were analysed using OLINK as described below.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:56:22.643.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rose Hodgson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	affinity proteomics

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-12 08:20:32	ID requested
⏵ 1	2025-05-07 06:56:23	announced

10.1158/1078-0432.ccr-20-0414;

10.1016/j.xcrm.2025.102041;

Sarker D, Plummer R, Meyer T, Sodergren MH, Basu B, Chee CE, Huang KW, Palmer DH, Ma YT, Evans TRJ, Spalding DRC, Pai M, Sharma R, Pinato DJ, Spicer J, Hunter S, Kwatra V, Nicholls JP, Collin D, Nutbrown R, Glenny H, Fairbairn S, Reebye V, Voutila J, Dorman S, Andrikakou P, Lloyd P, Felstead S, Vasara J, Habib R, Wood C, Saetrom P, Huber HE, Blakey DC, Rossi JJ, Habib N, , in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial. Clin Cancer Res, 26(15):3936-3946(2020) [pubmed]

Plummer R, Sodergren MH, Hodgson R, Ryan BM, Raulf N, Nicholls JP, Reebye V, Voutila J, Sinigaglia L, Meyer T, Pinato DJ, Sarker D, Basu B, Blagden S, Cook N, Jeffrey Evans TR, Yachnin J, Chee CE, Li D, El-Khoueiry A, Diab M, Huang KW, Pai M, Spalding D, Talbot T, Noel MS, Keenan B, Mahalingam D, Song MS, Grosso M, Arnaud D, Auguste A, Zacharoulis D, Storkholm J, McNeish I, Habib R, Rossi JJ, Habib NA, TIMEPOINT, a phase 1 study combining MTL-CEBPA with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumors. Cell Rep Med, 6(4):102041(2025) [pubmed]

submitter keyword: Human, cancer, plasma proteome, immunomodulatory

Bríd Ryan
contact affiliation	MiNA Therapeutics, United Kingdom
contact email	brid@minatx.com
lab head
Rose Hodgson
contact affiliation	MiNA Therapeutics
contact email	rose@minatx.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/2025/05/PXD060726

PRIDE project URI

• PRIDE
  1. PXD060726
     1. Label: PRIDE project
     2. Name: TIMEPOINT, a phase 1 study of MTL-CEBPA in combination with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumours.