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

• Published in: Clinical and experimental immunology Vol. 143; no. 2; pp. 314 - 321
• Main Authors: Van Keulen, V. P., Ciric, B., Radhakrishnan, S., Heckman, K. L., Mitsunaga, Y., Iijima, K., Kita, H., Rodriguez, M., Pease, L. R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2006; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: allergy; Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Biological and medical sciences; cancer; Cell Death - immunology; Cell Line; Clinical Studies; dendritic cells; Dendritic Cells - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Light Chains - immunology; Immunoglobulin M - immunology; Immunopathology; Interleukin-6 - immunology; Medical sciences; Melanoma - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Recombinant Proteins - immunology; Respiratory Hypersensitivity - immunology; T-Lymphocytes - immunology; therapy/immunotherapy; Transfection; Tumor Necrosis Factor-alpha - immunology; Waldenstrom Macroglobulinemia - immunology; Human; Immunopathology; Allergy; Dendritic cell; Antibody; Immunomodulation; Malignant tumor; therapy/immunotherapy; Immunology; Treatment; dendritic cells; Antigen presenting cell; Immunotherapy; B7 molecule; cancer; Recombinant protein
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02992.x

Summary 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.