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Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2: Coordination of dendritic and CD8(+) cell responses

  1. Author:
    Murphy, W. J.
    Welniak, L.
    Back, T.
    Hixon, J.
    Subleski, J.
    Seki, N.
    Wigginton, J. M.
    Wilson, S. E.
    Blazar, B. R.
    Malyguine, A. M.
    Sayers, T. J.
    Wiltrout, R. H.

  2. Author Address

    Univ Nevada, Sch Med, Dept Microbiol, ARF Room 342,Mail Stop 199, Reno, NV 89557 USA Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA Chiron Corp, Prot Therapeut, Emeryville, CA 94608 USA Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA Murphy WJ Univ Nevada, Sch Med, Dept Microbiol, ARF Room 342,Mail Stop 199, Reno, NV 89557 USA
    1. Year: 2003
  2. Journal: Journal of Immunology
    1. 170
    2. 5
    3. Pages: 2727-2733
  4. Type of Article: Article
  1. Abstract:

    In cancer, the coordinate engagement of professional APC and Ag-specific cell-mediated effector cells may be vital for the induction of effective antitumor responses. We speculated that the enhanced differentiation and function of dendritic cells through CD40 engagement combined with IL-2 administration to stimulate T cell expansion would act coordinately to enhance the adaptive immune response against cancer. In mice bearing orthotopic metastatic renal cell carcinoma, only the combination of an agonist Ab to CD40 and IL-2, but neither agent administered alone, induced complete regression of metastatic tumor and specific immunity to subsequent rechallenge in the majority of treated mice. The combination of anti-CD40 and IL-2 resulted in significant increases in dendritic cell and CD8(+) T cell number in advanced tumor- bearing mice compared with either agent administered singly. The antitumor effects of anti-CD40 and IL-2 were found to be dependent on CD8(+) T cells, IFN-gamma, IL-12 p40, and Fas ligand. CD40 stimulation and IL-2 may therefore be of use to promote antitumor responses in advanced metastatic cancer.

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