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dc.contributor.author
Wang, Jian
dc.contributor.author
Weiss, Tobias
dc.contributor.author
Neidert, Marian C.
dc.contributor.author
Toussaint, Nora Christina
dc.contributor.author
Naghavian, Reza
dc.contributor.author
Sellés-Moreno, Carla
dc.contributor.author
Foege, Magdalena
dc.contributor.author
Tomas-Ojer, Paula
dc.contributor.author
Medici, Gioele
dc.contributor.author
Jelcic, Ivan
dc.contributor.author
Schulz, Daniel
dc.contributor.author
Rushing, Elisabeth
dc.contributor.author
Dettwiler, Susanne
dc.contributor.author
Schrörs, Barbara
dc.contributor.author
Shin, Joo Heon
dc.contributor.author
McKay, Ron
dc.contributor.author
Wu, Catherine J.
dc.contributor.author
Lutterotti, Andreas
dc.contributor.author
Sospedra, Mireia
dc.contributor.author
Moch, Holger
dc.contributor.author
et al.
dc.date.accessioned
2023-01-17T09:46:30Z
dc.date.available
2023-01-01T04:59:39Z
dc.date.available
2023-01-17T07:56:54Z
dc.date.available
2023-01-17T09:46:30Z
dc.date.issued
2022-12-15
dc.identifier.issn
1078-0432
dc.identifier.issn
1557-3265
dc.identifier.other
10.1158/1078-0432.CCR-22-1741
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/589565
dc.identifier.doi
10.3929/ethz-b-000589565
dc.description.abstract
Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutations to enhance their immunogenicity. Experimental Design: Exome and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides. Subsequently, in silico HLA-anchor placements were used to deduce putative T-cell receptor (TCR) contacts of peptides. Single amino acids of TCR contacting residues were then mutated by amino acid replacements. Overall, 175 peptides were synthesized and sets of 25 each containing both peptides designed to bind to HLA class I and II molecules applied in the vaccination. Upon development of a tumor recurrence, the tumor-infiltrating lymphocytes (TIL) were characterized in detail both at the bulk and clonal level. Results: The immune response of peripheral blood T cells to vaccine peptides, including natural peptides and designed neopeptides, gradually increased with repetitive vaccination, but remained low. In contrast, at the time of tumor recurrence, CD8+ TILs and CD4+ TILs responded to 45% and 100%, respectively, of the vaccine peptides. Furthermore, TIL-derived CD4+ T-cell clones showed strong responses and tumor cell lysis not only against the designed neopeptide but also against the unmutated natural peptides of the tumor. Conclusions: Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T-cell responses in a cold tumor like glioblastoma.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Association for Cancer Research
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title
Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2022-10-13
ethz.journal.title
Clinical Cancer Research
ethz.journal.volume
28
en_US
ethz.journal.issue
24
en_US
ethz.journal.abbreviated
Clin Cancer Res
ethz.pages.start
5368
en_US
ethz.pages.end
5382
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Functional Role of the HLA-DR15 Haplotype in Multiple Sclerosis
en_US
ethz.identifier.scopus
ethz.publication.place
Philadelphia, PA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09735 - Bodenmiller, Bernd / Bodenmiller, Bernd
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02892 - NEXUS Personalized Health Technologies / NEXUS Personalized Health Technologies
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09735 - Bodenmiller, Bernd / Bodenmiller, Bernd
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02892 - NEXUS Personalized Health Technologies / NEXUS Personalized Health Technologies
ethz.grant.agreementno
340733
ethz.grant.fundername
EC
ethz.grant.funderDoi
10.13039/501100000780
ethz.grant.program
FP7
ethz.date.deposited
2023-01-01T04:59:40Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2023-01-17T07:56:57Z
ethz.rosetta.lastUpdated
2024-02-02T19:27:47Z
ethz.rosetta.versionExported
true
ethz.COinS
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