Publication: CD40 signaling drives potent cellular immune responses in heterologous cancer vaccinations
Issued Date
2017-04-15
Resource Type
ISSN
15387445
00085472
00085472
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2-s2.0-85018179484
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Mahidol University
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SCOPUS
Bibliographic Citation
Cancer Research. Vol.77, No.8 (2017), 1918-1926
Suggested Citation
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Gürlevik, Christine S. Falk, Michael P. Manns, Florian Kühnel, Thomas C. Wirth CD40 signaling drives potent cellular immune responses in heterologous cancer vaccinations. Cancer Research. Vol.77, No.8 (2017), 1918-1926. doi:10.1158/0008-5472.CAN-16-2089 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/41930
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Title
CD40 signaling drives potent cellular immune responses in heterologous cancer vaccinations
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Abstract
© 2017 American Association for Cancer Research. Antagonistic antibodies targeting coinhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited because of the insufficient induction of adaptive immune responses. Here, we describe a novel vaccination method consisting of a primary dendritic cell (DC) immunization followed by a composite vaccination, including an agonistic CD40 antibody, soluble antigen, and a TLR3 agonist, referred to as CoAT. In mice, DC/CoAT prime-boost vaccinations targeting eitherMHC class I or II neoantigens or tumor-Associated antigens rendered up to 60%of the total T-cell population specific for a single tumor epitope. DC/ CoAT induced durable and complete remissions of large subcutaneous tumors without detectable side effects. Thus, booster vaccinations with agonistic costimulatory antibodies represent an ideal means to amplify DC vaccinations and induce robust T-cell immune responses while providing maximumflexibility regarding the choice of antigen.