Co-transplantation of human hematopoietic stem cells and human breast cancer cells in NSG mice: A novel approach to generate tumor cell specific human antibodies

作者: Anja K Wege , Marcus Schmidt , Elke Ueberham , Marvin Ponnath , Olaf Ortmann

DOI: 10.4161/MABS.29111

关键词:

摘要: Humanized tumor mice (HTM) were generated by the co-transplantation of human hematopoietic stem cells and breast cancer overexpressing HER2 into neonatal NOD-scid IL2Rγ(null) (NSG) mice. These are characterized development a immune system in combination with growth. Due to concurrent transplantation newborn mice, transfer MHC-mismatched resulted solid coexistence cell activation (CD4(+) T cells, natural killer myeloid cells), but without evidence for rejection. Histological staining spleen HTM revealed co-localization antigen-presenting together B allowing MHC-dependent interaction, thereby generation cell-dependent antibody production. Here, we investigated capability these generate tumor-specific antibodies correlated immunoglobulin titers outgrowth. We found detectable IgM also IgG amounts serum HTM, which apparently controlled when concentrations above 10 µg/ml. Western blot analyses that did not recognize HER2/neu antigens, different, possibly relevant antigens therapy. In conclusion, offer novel approach complete monoclonal do require further genetic manipulation (e. g., humanization) potential application humans. addition, efficacy safety can be tested same mouse model under human-like conditions. This might particular interest subtypes no currently available

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