rWTC-MBTA Vaccine Induces Potent Adaptive Immune Responses Against Glioblastomas via Dynamic Activation of Dendritic Cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F24%3A43908623" target="_blank" >RIV/60076658:12310/24:43908623 - isvavai.cz</a>

Result on the web

<a href="https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202308280" target="_blank" >https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202308280</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/advs.202308280" target="_blank" >10.1002/advs.202308280</a>

Result language

angličtina

Original language name

rWTC-MBTA Vaccine Induces Potent Adaptive Immune Responses Against Glioblastomas via Dynamic Activation of Dendritic Cells

Original language description

Despite strides in immunotherapy, glioblastoma multiforme (GBM) remains challenging due to low inherent immunogenicity and suppressive tumor microenvironment. Converting &quot;cold&quot; GBMs to &quot;hot&quot; is crucial for immune activation and improved outcomes. This study comprehensively characterized a therapeutic vaccination strategy for preclinical GBM models. The vaccine consists of Mannan-BAM-anchored irradiated whole tumor cells, Toll-like receptor ligands [lipoteichoic acid (LTA), polyinosinic-polycytidylic acid (Poly (I:C)), and resiquimod (R-848)], and anti-CD40 agonistic antibody (rWTC-MBTA). Intracranial GBM models (GL261, SB28 cells) are used to evaluate the vaccine efficacy. A substantial number of vaccinated mice exhibited complete regression of GBM tumors in a T-cell-dependent manner, with no significant toxicity. Long-term tumor-specific immune memory is confirmed upon tumor rechallenge. In the vaccine-draining lymph nodes of the SB28 model, rWTC-MBTA vaccination triggered a major rise in conventional dendritic cell type 1 (cDC1) 12 h post-treatment, followed by an increase in conventional dendritic cell type 2 (cDC2), monocyte-derived dendritic cell (moDC), and plasmacytoid dendritic cell (pDC) on Day 5 and Day 13. Enhanced cytotoxicity of CD4+ and CD8+ T cells in vaccinated mice is verified in co-culture with tumor cells. Analyses of immunosuppressive signals (T-cell exhaustion, myeloid-derived suppressor cells (MDSC), M2 macrophages) in the GBM microenvironment suggest potential combinations with other immunotherapies for enhanced efficacy. In conclusion, the authors findings demonstrate that rWTC-MBTA induces potent and long-term adaptive immune responses against GBM. Representative histology images of brain tumor areas in the control group and vaccine (rGL261-MBTA) group on day 13 after the start of treatments. Small magnification. Scale bars, 600 mu m. High magnification of dashed rectangle area. Scale bar, 60 mu m. High magnification of indicated dashed rectangle areas. Red arrows indicate infiltrating lymphocytes. Scale bars, 60 mu m. image

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Advanced Science Letters

ISSN

1936-6612

e-ISSN

1936-7317

Volume of the periodical

11

Issue of the periodical within the volume

14

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

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UT code for WoS article

001154152700001

EID of the result in the Scopus database

2-s2.0-85183709827