Cell targeting and immunostimulatory properties of a novel Fcγ-receptor-independent agonistic anti-CD40 antibody in rhesus macaques
Yan X, Ols S, Arcoverde Cerveira R, Lenart K, Hellgren F, Ye K, Cagigi A, Buggert M, Nimmerjahn F, Falkesgaard Højen J, Parera D, Pessara U, Fischer S, Loré K (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 80
Article Number: 189
Journal Issue: 7
DOI: 10.1007/s00018-023-04828-2
Abstract
Targeting CD40 by agonistic antibodies used as vaccine adjuvants or for cancer immunotherapy is a strategy to stimulate immune responses. The majority of studied agonistic anti-human CD40 antibodies require crosslinking of their Fc region to inhibitory FcγRIIb to induce immune stimulation although this has been associated with toxicity in previous studies. Here we introduce an agonistic anti-human CD40 monoclonal IgG1 antibody (MAB273) unique in its specificity to the CD40L binding site of CD40 but devoid of Fcγ-receptor binding. We demonstrate rapid binding of MAB273 to B cells and dendritic cells resulting in activation in vitro on human cells and in vivo in rhesus macaques. Dissemination of fluorescently labeled MAB273 after subcutaneous administration was found predominantly at the site of injection and specific draining lymph nodes. Phenotypic cell differentiation and upregulation of genes associated with immune activation were found in the targeted tissues. Antigen-specific T cell responses were enhanced by MAB273 when given in a prime-boost regimen and for boosting low preexisting responses. MAB273 may therefore be a promising immunostimulatory adjuvant that warrants future testing for therapeutic and prophylactic vaccination strategies.
Authors with CRIS profile
Involved external institutions
Karolinska University Hospital / Karolinska Universitetssjukhuset
Sweden (SE)
Karolinska Institute
Sweden (SE)
Aarhus University Hospital / Aarhus Universitetshospital
Denmark (DK)
MAB Discovery GmbH
Germany (DE)
Sweden (SE)
Karolinska Institute
Sweden (SE)
Aarhus University Hospital / Aarhus Universitetshospital
Denmark (DK)
MAB Discovery GmbH
Germany (DE)
How to cite
APA:
Yan, X., Ols, S., Arcoverde Cerveira, R., Lenart, K., Hellgren, F., Ye, K.,... Loré, K. (2023). Cell targeting and immunostimulatory properties of a novel Fcγ-receptor-independent agonistic anti-CD40 antibody in rhesus macaques. Cellular and Molecular Life Sciences, 80(7). https://dx.doi.org/10.1007/s00018-023-04828-2
MLA:
Yan, Xianglei, et al. "Cell targeting and immunostimulatory properties of a novel Fcγ-receptor-independent agonistic anti-CD40 antibody in rhesus macaques." Cellular and Molecular Life Sciences 80.7 (2023).
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