A replicating LCMV-based vaccine for the treatment of solid tumors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F24%3A00135312" target="_blank" >RIV/00216224:14110/24:00135312 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S1525001623006597?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1525001623006597?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ymthe.2023.11.026" target="_blank" >10.1016/j.ymthe.2023.11.026</a>
Alternative languages
Result language
angličtina
Original language name
A replicating LCMV-based vaccine for the treatment of solid tumors
Original language description
Harnessing the immune system to eradicate tumors requires identification and targeting of tumor antigens, including tumor-specific neoantigens and tumor-associated self-antigens. Tumor-associated antigens are subject to existing immune tolerance, which must be overcome by immunotherapies. Despite many novel immunotherapies reaching clinical trials, inducing self-antigen-specific immune responses remains challenging. Here, we systematically investigate viral-vector-based cancer vaccines encoding a tumor-associated self-antigen (TRP2) for the treatment of established melanomas in preclinical mouse models, alone or in combination with adoptive T cell therapy. We reveal that, unlike foreign antigens, tumor-associated antigens require replication of lymphocytic choriomeningitis virus (LCMV)-based vectors to break tolerance and induce effective antigen-specific CD8+ T cell responses. Immunization with a replicating LCMV vector leads to complete tumor rejection when combined with adoptive TRP2-specific T cell transfer. Importantly, immunization with replicating vectors leads to extended antigen persistence in secondary lymphoid organs, resulting in efficient T cell priming, which renders previously “cold” tumors open to immune infiltration and reprograms the tumor microenvironment to “hot.” Our findings have important implications for the design of next-generation immunotherapies targeting solid cancers utilizing viral vectors and adoptive cell transfer.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Therapy
ISSN
1525-0016
e-ISSN
1525-0024
Volume of the periodical
32
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
426-439
UT code for WoS article
001193286100001
EID of the result in the Scopus database
2-s2.0-85180497920