Fcγ-Receptor-Independent Controlled Activation of CD40 Canonical Signaling by Novel Therapeutic Antibodies for Cancer Therapy

Beckmann K, Reitinger C, Yan X, Carle A, Blümle E, Jurkschat N, Paulmann C, Prassl S, Kazandjian LV, Loré K, Nimmerjahn F, Fischer S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Antibodies MDPI

Book Volume: 13

Article Number: 31

Journal Issue: 2

DOI: 10.3390/antib13020031

Abstract

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.

Authors with CRIS profile

Carmen Reitinger Lehrstuhl für Genetik Falk Nimmerjahn Lehrstuhl für Genetik

Involved external institutions

BioNTech / Biopharmaceutical New Technologies DE Germany (DE) Karolinska University Hospital / Karolinska Universitetssjukhuset SE Sweden (SE)

How to cite

APA:

Beckmann, K., Reitinger, C., Yan, X., Carle, A., Blümle, E., Jurkschat, N.,... Fischer, S. (2024). Fcγ-Receptor-Independent Controlled Activation of CD40 Canonical Signaling by Novel Therapeutic Antibodies for Cancer Therapy. Antibodies, 13(2). https://doi.org/10.3390/antib13020031

MLA:

Beckmann, Karsten, et al. "Fcγ-Receptor-Independent Controlled Activation of CD40 Canonical Signaling by Novel Therapeutic Antibodies for Cancer Therapy." Antibodies 13.2 (2024).

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