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Such therapies may be augmented by providing tumor antigen in the form of cancer vaccines. Our aim was to study the effects of mitazalimab (ADC-1013; JNJ-64457107), a human anti-CD40 agonist IgG1 antibody, on activation of antigen-presenting cells, and how this influences the priming and anti-tumor potential of antigen-specific T cells, in mice transgenic for human CD40. Mitazalimab activated splenic CD11c<jats:sup>+<\/jats:sup> MHCII<jats:sup>+<\/jats:sup> dendritic cells and CD19<jats:sup>+<\/jats:sup> MHCII<jats:sup>+<\/jats:sup> B cells within 6\u00a0h, with a return to baseline within 1\u00a0week. This was associated with a dose-dependent release of proinflammatory cytokines in the blood, including IP-10, MIP-1\u03b1 and TNF-\u03b1. Mitazalimab administered at different dose regimens with ovalbumin protein showed that repeated dosing expanded ovalbumin peptide (SIINFEKL)-specific CD8<jats:sup>+<\/jats:sup> T cells and increased the frequency of activated ICOS<jats:sup>+<\/jats:sup> T cells and CD44<jats:sup>hi<\/jats:sup> CD62L<jats:sup>\u2212<\/jats:sup> effector memory T cells in the spleen. Mitazalimab prolonged survival of mice bearing MB49 bladder carcinoma tumors and increased the frequency of activated granzyme B<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells in the tumor. In the ovalbumin-transfected tumor E.G7-OVA lymphoma, mitazalimab administered with either ovalbumin protein or SIINFEKL peptide prolonged the survival of E.G7-OVA tumor-bearing mice, as prophylactic and therapeutic treatment. Thus, mitazalimab activates antigen-presenting cells, which improves expansion and activation of antigen-specific T cells and enhances the anti-tumor efficacy of a model cancer vaccine.<\/jats:p>","DOI":"10.1007\/s00262-021-02932-5","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T02:02:29Z","timestamp":1620180149000},"page":"3629-3642","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The human anti-CD40 agonist antibody mitazalimab (ADC-1013; JNJ-64457107) activates antigen-presenting cells, improves expansion of antigen-specific T cells, and enhances anti-tumor efficacy of a model cancer vaccine in vivo"],"prefix":"10.1007","volume":"70","author":[{"given":"Adnan","family":"Deronic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneli","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Thagesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doreen","family":"Werchau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Enell Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-1250","authenticated-orcid":false,"given":"Peter","family":"Ellmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"2932_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/bjc.2017.136","volume":"117","author":"AP Cogdill","year":"2017","unstructured":"Cogdill AP, Andrews MC, Wargo JA (2017) Hallmarks of response to immune checkpoint blockade. 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