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CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help

Nature Medicine volume 5, pages 548–553 (1999)Cite this article

Abstract

CD40 is essential in enabling antigen-presenting cells to process and present antigen effectively to T cells. We demonstrate here that when antibody against CD40 is used to treat mice with syngeneic lymphoma, a rapid cytotoxic T-cell response independent of T-helper cells occurs, with tenfold expansion of CD8+ T cells over a period of 5 days. This response eradicates the lymphoma and provides protection against tumor rechallenge without further antibody treatment. Thus, it seems that by treating mice with monoclonal antibody against CD40, we are immunizing against syngeneic tumors. The phenomenon proved reproducible with two antibodies against CD40 (3/23 and FGK-45) in three CD40+ lymphomas (A20, A31 and BCL1) and gave partial protection in one of two CD40– lymphomas (EL4 and Ten1). Although the nature of the target antigens on these lymphomas is unknown, CD8+ T cells recovered from responding mice showed powerful cytotoxic activity against the target B-cell lymphoma in vitro.

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Figure 1: The therapeutic activity of anti-CD40 monoclonal antibody requires an intact immune system.
Figure 2: CD40 monoclonal antibody therapy is very active against CD40+ B-cell lymphomas and partially effective against some CD 40– T-cell lymphomas.
Figure 3: The therapeutic activity of monoclonal antibody against CD40 depends on CD8+, but not CD4+, T cells.
Figure 4: Changes in normal lymphocytes and cytokine mRNA profiles after treatment of lymphoma-bearing mice with monoclonal antibody against CD40.
Figure 5: Killing of lymphoma by splenic lymphocytes isolated from tumor-bearing mice treated with monoclonal antibody against CD40 .

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Acknowledgements

We thank S. Cobbold for advice and monoclonal antibody for the T-cell depletion work. We also thank A. Al-Shamkhani, T. Hamblin, T. Illidge, P. Johnson, K. Roberts, D. Mason, G. Stevenson and colleagues from Tenovus for suggestions and critical evaluation of the manuscript. This work has been supported by grants from Tenovus Cardiff, the Leukaemia Research Fund and the the European Union.

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  1. Lymphoma Research Unit, Tenovus Laboratory, General Hospital, Southampton, SO16 6YD, UK

    Ruth R. French, H.T. Claude Chan, Alison L. Tutt & Martin J. Glennie

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  1. Ruth R. French
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Correspondence to Martin J. Glennie.

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French, R., Chan, H., Tutt, A. et al. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat Med 5, 548–553 (1999). https://doi.org/10.1038/8426

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