PXD005426 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Human, Phosphoproteomics, CAR, LC-MS/MS |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD005426
- Label: PRIDE project
- Name: Concert between cytokines and costimulatory domains to optimize chimeric antigen receptor immunotherapy in neuroblastoma model