PXD005426

PXD005426 is an original dataset announced via ProteomeXchange.

Title	Concert between cytokines and costimulatory domains to optimize chimeric antigen receptor immunotherapy in neuroblastoma model
Description	Adoptive T cell therapy with gene-modified T cells expressing chimeric antigen receptor (CAR) is a rapidly growing field of translational medicine and recently has shown dramatic therapeutic success in the treatment of B-cell malignancies. However, challenges to achieve similar response in patients harboring solid tumour are still considerable. To achieve anti-tumor efficacy, these cells must survive, expand and persist after infusion into patients. An important lesson has been derived from clinical trials using CAR technologies: the relevance of the CAR design to enhance signaling and sustain T cell proliferation and survival. Here, we prove that third generation CARs specific for GD2 antigen incorporating CD28.4-1BB costimulatory domains improves T cell immunotherapy in a neuroblastoma (NB) pre-clinical model, as compared to a CAR with the same specificity but including CD28.OX40 costimulation. Indeed, we test the anti-tumor activity of polyclonal T cells genetically modified with third generation CAR.GD2 incorporating either CD28.4-1BB or CD28.OX40 in frame with the safety switch inducible Caspase 9 (iC9). We prove a significant in vitro and in vivo amelioration of the approach by the presence of 4.1BB signaling in terms of: 1) less T cell exhaustion, 2) lower basal T cell activation, 3) higher in vivo tumor control and 4) T cell persistence. In addition, the fine tuning of T cell culture conditions with the use of IL7 and IL15 show to be synergic with the third generation CAR.GD2 design to optimize CAR T immunotherapy for NB. Our results provide a proof-of-concept for the need to optimize not only CAR construct design but also T cell culture conditions in order to boost T cell activity in vivo.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:34:38.833.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Petretto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-11-23 02:58:31	ID requested
1	2018-06-27 08:41:19	announced
2	2020-11-17 07:46:06	announced	2020-11-17: Updated publication reference for PubMed record(s): 29872565.
⏵ 3	2024-10-22 04:34:46	announced	2024-10-22: Updated project metadata.

10.1080/2162402x.2018.1433518;

Quintarelli C, Orlando D, Boffa I, Guercio M, Polito VA, Petretto A, Lavarello C, Sinibaldi M, Weber G, Del Bufalo F, Giorda E, Scarsella M, Petrini S, Pagliara D, Locatelli F, De Angelis B, Caruana I, Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma. Oncoimmunology, 7(6):e1433518(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, Phosphoproteomics, CAR, LC-MS/MS

Andrea Petretto
contact affiliation	Laboratorio Core Facilities Gaslini Children's Hospital
contact email	andreapetretto@gaslini.org
lab head
Andrea Petretto
contact affiliation	Gaslini Children's Hospital
contact email	a.petretto@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/2018/06/PXD005426

PRIDE project URI

• PRIDE
  1. PXD005426
     1. Label: PRIDE project
     2. Name: Concert between cytokines and costimulatory domains to optimize chimeric antigen receptor immunotherapy in neuroblastoma model