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Generation of a human IgM monoclonal antibody directed against HLA class II molecules: a potential agent in the treatment of haematological malignancies

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Abstract

Major histocompatibility complex (MHC) class II molecules have been considered as a good target molecule for use in immunotherapy, because of the high expression in some lymphoma and leukaemia cells and, also, because of their restricted expression on human cells (monocytes, dendritic, B lymphocytes, thymic epithelial cells, and some cytokine-activated cells, such as T lymphocytes). We have obtained a human IgM monoclonal antibody directed against human leukocyte antigen (HLA) class II molecules, using transgenic mice carrying human Ig genes. The antibody BH1 (IgM/κ isotype) recognises HLA-class II on the surface of tumour cells from patients suffering from haematological malignancies, such as chronic and acute lymphocytic leukaemias, non-Hodgkin lymphomas and myeloid leukaemias. Interestingly, functional studies revealed that BH1 mAb recognises and kills very efficiently tumour cells from several leukaemia patients in the presence of human serum as a source of complement. These results suggest that this human IgM monoclonal antibody against HLA-class II could be considered as a potential agent in the treatment of several malignancies.

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Acknowledgments

We would like to thank Dr Marianne Brüggemann for supplying the transgenic mice used in this work; Angel Torreiro for assistance with maintenance of the mice; Charo de Pablo (Clínica Puerta de Hierro, Madrid) and Professor Alan Epstein (University of Southern California, USA) for providing antibodies Q2/70 and CHLym-1, respectively; and Darío Alves, Cristian Sánchez, Daniel Pérez, Elina Garet, Silvia Lorenzo and Marisa Abad for technical help. The contributions of B. D. and I. S. include the generation and characterisation of monoclonal antibodies, analysis of peripheral blood cells and complement lysis. S. M. performed most of the flow cytometry studies in different populations and supervised the complement lysis and analysis in leukaemia patients. F. G. and A. G. supervised the work undertaken by B. D., I. S. and S. M. in the Hospital and in the University, respectively. This study was supported by the Xunta de Galicia, the Instituto de Salud Carlos III (Red del FIS G03/136) and the Ministerio de Educación y Ciencia (Nanobiomed, Consolider-Ingenio2010).

Conflict of interest statement

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Immunology Unit, Universidad de Vigo, Edificio de Ciencias Experimentales, Campus Lagoas Marcosende, s/n, 36310, Vigo, Pontevedra, Spain

    Belén Díaz & África González–Fernández

  2. Immunology Unit, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, 36300, Vigo, Pontevedra, Spain

    Irene Sanjuan & Francisco Gambón

  3. Hematology Unit, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, 36300, Vigo, Pontevedra, Spain

    Carmen Loureiro

  4. Instituto Superior de Saude do Alto Ave (ISAVE), Quinta de Matos, Geraz do Minho, 4830-31, PVL, Portugal

    Susana Magadán

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  1. Belén Díaz
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  2. Irene Sanjuan
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  3. Francisco Gambón
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  4. Carmen Loureiro
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  6. África González–Fernández
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Correspondence to Belén Díaz.

Additional information

Belén Díaz, Irene Sanjuan and Susana Magadán share authorship; Francisco Gambón and África González–Fernández share leadership.

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Díaz, B., Sanjuan, I., Gambón, F. et al. Generation of a human IgM monoclonal antibody directed against HLA class II molecules: a potential agent in the treatment of haematological malignancies. Cancer Immunol Immunother 58, 351–360 (2009). https://doi.org/10.1007/s00262-008-0558-6

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  • DOI: https://doi.org/10.1007/s00262-008-0558-6

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