Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12

V. P. Van Keulen, B. Ciric, S. Radhakrishnan, K. L. Heckman, Y. Mitsunaga, K. Iijima, H. Kita, M. Rodriguez, L. R. Pease

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

A patient with Waldenstrom's macroglobulinaemia expresses a high titre IgM antibody in serum that binds both mouse and human dendritic cells (DC) in a B7-DC (PD-L2)-dependent manner. We have reported previously that purified antibody from patient serum activates immature and mature DC in vitro, enhancing the ability of these professional antigen-presenting cells to activate naive T cells, take up antigen, resist a cytokine-depleted environment and secrete immunomodulatory cytokines, such as interkeukin (IL)-6 and tumour necrosis factor (TNF)-α. Systemic treatment of experimental animals with this antibody induces potent anti-melanoma immunity and modulates protectively the recall response against antigen challenge through the airway in an experimental model of inflammatory airway disease. Here we describe a monoclonal IgM antibody derived from this serum immunoglobulin that recapitulates each of these earlier observations, providing direct evidence that M protein from the Waldenstrom's patient mediates these potent immunomodulatory effects. Furthermore, cell lines expressing this recombinant form of the human antibody provide the basis for developing this reagent for clinical application.

Original languageEnglish (US)
Pages (from-to)314-321
Number of pages8
JournalClinical and Experimental Immunology
Volume143
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Allergy
  • Cancer
  • Dendritic cells
  • Therapy/immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Van Keulen, V. P., Ciric, B., Radhakrishnan, S., Heckman, K. L., Mitsunaga, Y., Iijima, K., Kita, H., Rodriguez, M., & Pease, L. R. (2006). Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12. Clinical and Experimental Immunology, 143(2), 314-321. https://doi.org/10.1111/j.1365-2249.2005.02992.x