| Autor: |
Karsten Beckmann, Carmen Reitinger, Xianglei Yan, Anna Carle, Eva Blümle, Nicole Jurkschat, Claudia Paulmann, Sandra Prassl, Linda V. Kazandjian, Karin Loré, Falk Nimmerjahn, Stephan Fischer |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Antibodies, Vol 13, Iss 2, p 31 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2073-4468 |
| DOI: |
10.3390/antib13020031 |
| Popis: |
The activation of CD40-mediated signaling in antigen-presenting cells is a promising therapeutic strategy to promote immune responses against tumors. Most agonistic anti-CD40 antibodies currently in development require the Fcγ-receptor (FcγR)-mediated crosslinking of CD40 molecules for a meaningful activation of CD40 signaling but have limitations due to dose-limiting toxicities. Here we describe the identification of CD40 antibodies which strongly stimulate antigen-presenting cells in an entirely FcγR-independent manner. These Fc-silenced anti-CD40 antibodies induce an efficient upregulation of costimulatory receptors and cytokine release by dendritic cells. Finally, the most active identified anti-CD40 antibody shows activity in humanized mice. More importantly, there are no signs of obvious toxicities. These studies thus demonstrate the potent activation of antigen-presenting cells with anti-CD40 antibodies lacking FcγR-binding activity and open the possibility for an efficacious and safe combination therapy for cancer patients. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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