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

William J Murphy, Lisbeth Welniak, Timothy Back, Julie Hixon, Jeff Subleski, Naoko Seki, Jon M. Wigginton, Susan E. Wilson, Bruce R. Blazar, Anatoli M. Malyguine, Thomas J. Sayers, Robert H. Wiltrout

Research output: Contribution to journalArticle

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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-γ, IL-12 p40, and Fas ligand. CD40 stimulation and IL-2 may therefore be of use to promote antitumor responses in advanced metastatic cancer.

Original languageEnglish (US)
Pages (from-to)2727-2733
Number of pages7
JournalJournal of Immunology
Volume170
Issue number5
StatePublished - Mar 1 2003
Externally publishedYes

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Dendritic Cells
Interleukin-2
Antibodies
Neoplasms
T-Lymphocytes
Fas Ligand Protein
Adaptive Immunity
Interleukin-12
Renal Cell Carcinoma
Immunity
Cell Count

ASJC Scopus subject areas

  • Immunology

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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. / Murphy, William J; Welniak, Lisbeth; Back, Timothy; Hixon, Julie; Subleski, Jeff; Seki, Naoko; Wigginton, Jon M.; Wilson, Susan E.; Blazar, Bruce R.; Malyguine, Anatoli M.; Sayers, Thomas J.; Wiltrout, Robert H.

In: Journal of Immunology, Vol. 170, No. 5, 01.03.2003, p. 2727-2733.

Research output: Contribution to journalArticle

Murphy, WJ, Welniak, L, Back, T, Hixon, J, Subleski, J, Seki, N, Wigginton, JM, Wilson, SE, Blazar, BR, Malyguine, AM, Sayers, TJ & Wiltrout, RH 2003, 'Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2: Coordination of dendritic and CD8+ cell responses', Journal of Immunology, vol. 170, no. 5, pp. 2727-2733.
Murphy, William J ; Welniak, Lisbeth ; Back, Timothy ; Hixon, Julie ; Subleski, Jeff ; Seki, Naoko ; Wigginton, Jon M. ; Wilson, Susan E. ; Blazar, Bruce R. ; Malyguine, Anatoli M. ; Sayers, Thomas J. ; Wiltrout, Robert H. / Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2 : Coordination of dendritic and CD8+ cell responses. In: Journal of Immunology. 2003 ; Vol. 170, No. 5. pp. 2727-2733.
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