PXD044799-1

PXD044799 is an original dataset announced via ProteomeXchange.

Title	Neoantigen targeted dendritic cell vaccine generates durable T cell responses exhibiting the full spectrum of differentiation states in NSCLC patients
Description	Background. Dendritic cell (DC)-based neoantigen vaccination holds potential as a safe and effective adjuvant therapy for patients with early-stage, resectable NSCLC, a tumor type typically characterized by high mutational loads. DCs have the unique ability to elicit robust antitumoral T-cell responses, while neoantigens are ideal targets to elicit high-affinity T cell responses with exquisite tumor specificity. Here, we present the results of a phase I clinical trial in which a novel DC vaccine targeting neoantigens was evaluated in six patients with early stage, resected NSCLC. Methods. Tumor samples were subjected to a comprehensive neoantigen identification approach encompassing genomics, transcriptomics and immunopeptidomics. Patients underwent leukapheresis for the manufacturing of monocyte-derived DCs loaded with neoantigens (Neo-mDCs) according to a four-day protocol. Neo-mDCs were injected intravenously following an intrapatient dose escalation scheme. Primary endpoint of the trial was safety. Secondary endpoints were feasibility, immunogenicity, and relapse-free survival. As a quality control, dendritic cells transfected with the mRNA-encoded neoantigen were analyzed by shotgun proteomics to validate expression of the mRNA-encoded neoantigen. Results. The vaccine was demonstrated to be feasible and safe. T cell responses were observed in 5 of 6 vaccinated patients and were dominated by CD8+ T cells, which could be detected ex vivo at high frequencies >1.5 years after the last dose. Furthermore, single cell analysis indicated that the CD8+ T cell responsive population was polyclonal and exhibited the near entire spectrum of T cell differentiation states, including a naïve-like state associated with long lasting memory. Additionally, mRNA-encoded neoantigen were detected by shotgun proteomics in four patients out of the six patients that were tested.
HostingRepository	PRIDE
AnnounceDate	2024-03-17
AnnouncementXML	Submission_2024-03-17_03:51:53.389.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD044799
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fabien Thery
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 07:26:40	ID requested
⏵ 1	2024-03-17 03:51:53	announced
2	2024-10-22 06:33:45	announced	2024-10-22: Updated project metadata.

10.6019/PXD044799;

submitter keyword: cancer, lung non-small cell carcinoma, vaccine, neoantigen,human

Prof. Francis Impens
contact affiliation	Francis Impens, VIB-UGent Center for Medical Biotechnology, Ghent, Belgium.Department of Biomolecular Medicine, Ghent, Belgium. VIB Proteomics Core, Ghent, Belgium
contact email	francis.impens@vib-ugent.be
lab head
Fabien Thery
contact affiliation	VIB-UGent
contact email	fabien.thery91@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044799
     1. Label: PRIDE project
     2. Name: Neoantigen targeted dendritic cell vaccine generates durable T cell responses exhibiting the full spectrum of differentiation states in NSCLC patients