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
(2021) In Cancer Immunology, Immunotherapy 70(12). p.3629-3642- Abstract
Non-responders to checkpoint inhibitors generally have low tumor T cell infiltration and could benefit from immunotherapy that activates dendritic cells, with priming of tumor-reactive T cells as a result. 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+ MHCII+ dendritic cells and CD19+ MHCII+ B cells within 6 h, with a return to baseline... (More)
Non-responders to checkpoint inhibitors generally have low tumor T cell infiltration and could benefit from immunotherapy that activates dendritic cells, with priming of tumor-reactive T cells as a result. 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+ MHCII+ dendritic cells and CD19+ MHCII+ B cells within 6 h, with a return to baseline within 1 week. This was associated with a dose-dependent release of proinflammatory cytokines in the blood, including IP-10, MIP-1α and TNF-α. Mitazalimab administered at different dose regimens with ovalbumin protein showed that repeated dosing expanded ovalbumin peptide (SIINFEKL)-specific CD8+ T cells and increased the frequency of activated ICOS+ T cells and CD44hi CD62L− 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+ CD8+ 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.
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- author
- Deronic, Adnan LU ; Nilsson, Anneli ; Thagesson, Mia ; Werchau, Doreen ; Enell Smith, Karin LU and Ellmark, Peter LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cancer immunotherapy, Cancer vaccine, CD40 agonist antibody, Dendritic cell activation
- in
- Cancer Immunology, Immunotherapy
- volume
- 70
- issue
- 12
- pages
- 3629 - 3642
- publisher
- Springer
- external identifiers
-
- scopus:85105958449
- pmid:33948686
- ISSN
- 0340-7004
- DOI
- 10.1007/s00262-021-02932-5
- language
- English
- LU publication?
- yes
- id
- a375ed11-c99a-49bd-8e0d-ba2d0e80369d
- date added to LUP
- 2021-06-02 11:30:59
- date last changed
- 2024-06-15 11:59:57
@article{a375ed11-c99a-49bd-8e0d-ba2d0e80369d,
abstract = {{<p>Non-responders to checkpoint inhibitors generally have low tumor T cell infiltration and could benefit from immunotherapy that activates dendritic cells, with priming of tumor-reactive T cells as a result. 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<sup>+</sup> MHCII<sup>+</sup> dendritic cells and CD19<sup>+</sup> MHCII<sup>+</sup> B cells within 6 h, with a return to baseline within 1 week. This was associated with a dose-dependent release of proinflammatory cytokines in the blood, including IP-10, MIP-1α and TNF-α. Mitazalimab administered at different dose regimens with ovalbumin protein showed that repeated dosing expanded ovalbumin peptide (SIINFEKL)-specific CD8<sup>+</sup> T cells and increased the frequency of activated ICOS<sup>+</sup> T cells and CD44<sup>hi</sup> CD62L<sup>−</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<sup>+</sup> CD8<sup>+</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.</p>}},
author = {{Deronic, Adnan and Nilsson, Anneli and Thagesson, Mia and Werchau, Doreen and Enell Smith, Karin and Ellmark, Peter}},
issn = {{0340-7004}},
keywords = {{Cancer immunotherapy; Cancer vaccine; CD40 agonist antibody; Dendritic cell activation}},
language = {{eng}},
number = {{12}},
pages = {{3629--3642}},
publisher = {{Springer}},
series = {{Cancer Immunology, Immunotherapy}},
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}},
url = {{http://dx.doi.org/10.1007/s00262-021-02932-5}},
doi = {{10.1007/s00262-021-02932-5}},
volume = {{70}},
year = {{2021}},
}