PXD041256

PXD041256 is an original dataset announced via ProteomeXchange.

Title	Targeted delivery of tumor necrosis factor in combination with lomustine induces a T-cell dependent regression of glioblastoma
Description	Glioblastoma is the most aggressive primary brain tumor with an unmet need for more effective therapies. Here we report that the combination of L19TNF, an antibody-cytokine fusion protein based on tumor necrosis factor that selectively localizes on the tumor neo-vasculature, with the alkylating agent lomustine, can induce tumor regression in orthotopic glioma-bearing mice and patients with recurrent glioblastoma. Mechanistically, this striking synergy crucially depended on T cells and involved activation of the tumor endothelium, tumor DNA damage, treatment-associated tumor necrosis, increased antigen presentation on MHC class I and tumor immune cell infiltration, as well as decreased tumor-associated immunosuppression. The clinical translation of this approach is ongoing, but already shows durable responses in the first recurrent glioblastoma patient cohort treated with L19TNF in combination with lomustine (NCT04573192).
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:23.381.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041256
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Domenico Ravazza
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-31 08:37:23	ID requested
1	2023-06-01 02:13:16	announced
⏵ 2	2023-11-14 09:00:23	announced	2023-11-14: Updated project metadata.

10.6019/PXD041256;

submitter keyword: immunotherapy MHC-I,immunopeptidomics

Ettore Gilardoni
contact affiliation	Philochem AG,Libernstrasse 3, 8112 Otelfingen, Switzerland
contact email	ettore.gilardoni@philochem.ch
lab head
Domenico Ravazza
contact affiliation	Philochem AG
contact email	domenico.ravazza@philochem.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041256
     1. Label: PRIDE project
     2. Name: Targeted delivery of tumor necrosis factor in combination with lomustine induces a T-cell dependent regression of glioblastoma