title: Human antibodies targeting CD30(+) lymphomas.
abstract: Hodgkin- and Non-Hodgkin lymphomas are tumors of the lymphatic system, whose common therapy is chemotherapy and radiation. Immunotherapies with monoclonal antibodies are a promising strategy for treatment of malignant lymphomas and may overcome strong side effects and partial failure of and high relapse rates after common treatment. The antigen CD30 is overexpressed in Hodgkin lymphomas and some Non-Hodgkin lymphomas like anaplastic large cell lymphomas and adult T-cell lymphomas, which makes it a suitable target for antibody-based therapies. We isolated four new CD30-specific antibodies from a human naïve antibody gene library by phage display. These recombinant antibodies were produced as scFv in Escherichia coli and as bivalent immunoglobuline-like scFv-Fc antibodies in mammalian cells. They bound with high specificity to both recombinant antigen CD30 and to CD30(+) lymphoma cells. Flow cytometry and confocal laser scanning microscopy were used to show intracellular uptake by receptor-mediated endocytosis into CD30(+) lymphoma cell line Karpas299. The antibody clone SH313-B5 inhibited the proliferation of CD30(+) Karpas299 cells in a dose-dependent and effector independent manner with an IC(50) of 100 nM. Therefore, the antibody SH313-B5 is a promising candidate for further development towards treatment of CD30(+) tumors.
authors.affiliation: Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics, Braunschweig, Germany.
authors.forename: Xenia
authors.initials: X
authors.lastname: Wezler
authors.forename: Michael
authors.initials: M
authors.lastname: Hust
authors.forename: Saskia
authors.initials: S
authors.lastname: Helmsing
authors.forename: Thomas
authors.initials: T
authors.lastname: Schirrmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Dübel
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D019151:Peptide Library; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen; D019151:Peptide Library; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies