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Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmune inflammatory process

Abstract

The use of agonistic monoclonal antibody against CD40 has emerged as one the most effective ways to boost immune responses against infectious agents or to fight cancer. Here, we report that the same monoclonal antibodies against CD40 (FGK45 and 3/23) previously used to elicit protective immune responses treated the autoimmune inflammatory process of chronic collagen-induced arthritis in DBA/1–TCR-β transgenic mice, as well as collagen-induced arthritis in DBA/1 mice, both animal models of rheumatoid arthritis. This study indicates that agonistic monoclonal antibody against CD40 can potentially be used to treat chronic autoimmune inflammatory processes.

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Figure 1: Therapy of CCIA with agonistic monoclonal antibody against CD40 ameliorates established arthritis.
Figure 2: Long-term therapy with monoclonal antibodies against CD40 successfully controls the evolution of arthritis in mice.
Figure 3: Histological evaluation of monoclonal antibody against CD40 therapy.
Figure 4: Therapy with agonistic monoclonal antibody against CD40 alters the cytokine profile of antigen-specific activated T lymphocytes.
Figure 5: Treatment with monoclonal antibody against CD40 induces a specific reduction in synthesis of IFN-γ by CD4+ T lymphocytes.
Figure 6: Stimulation of CD40, with an agonistic monoclonal antibody, before immunization does not alter the course of CCIA.

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Acknowledgements

We thank T. Rolink for his support on this project, P. Warden and M. Medghalchi for their assistance in handling mice. The Arthritis and Rheumatism Campaign, UK, supports the Kennedy Institute of Rheumatology.

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Correspondence to Marco Londei.

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Mauri, C., Mars, L. & Londei, M. Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmune inflammatory process. Nat Med 6, 673–679 (2000). https://doi.org/10.1038/76251

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