GPC Biotech AG, Martinsried/Munich, Germany. zoltan.nagy@gpc-biotech.com
The Human Combinatorial Antibody Library (HuCAL) was screened for antibodies specific to human leukocyte antigen-DR (HLA-DR) that induce programmed death of lymphoma/leukemia cells expressing the target antigen. The active Fab fragments were affinity-matured, and engineered to IgG(4) antibodies of sub-nanomolar affinity. The antibodies exhibited potent in vitro tumoricidal activity on several lymphoma and leukemia cell lines and on chronic lymphocytic leukemia patient samples. They were also active in vivo in xenograft models of non-Hodgkin lymphoma. Cell death occurred rapidly, without the need for exogenous immunological effector mechanisms, and was selective to activated/tumor-transformed cells. Although the expression of HLA-DR on normal hematopoietic cells is a potential safety concern, the antibodies caused no long-lasting hematological toxicity in primates, in vivo. Such monoclonal antibodies offer the potential for a novel therapeutic approach to lymphoid malignancies.
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Der GPC-AK-Konkurrent Rituxan hat CD20 als Target... ist es ein Vorteil für den MHCII-AK, dass er mit dem Target HLA-DR an ein breiteres Spektrum von B-Cell-Typen andocken kann? ... Stammzellen und Pro-BZellen? (das ist wohl eher was für einen Fachmann... na Herr Professor, wie wäre es?)
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Angehängte Grafik:
HLA.JPG (verkleinert auf 59%)
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