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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-11-26)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-11-26)
    Abstract: The B-cell receptor (BCR) is a key player of the adaptive immune system. It is a unique part of immunoglobulin (Ig) molecules expressed on the surface of B cells. In case of many B-cell lymphomas, the tumor cells express a tumor-specific and functionally active BCR, also known as idiotype. Utilizing the idiotype as target for lymphoma therapy has emerged to be demanding since the idiotype differs from patient to patient. Previous studies have shown that shark-derived antibody domains (vNARs) isolated from a semi-synthetic CDR3-randomized library allow for the rapid generation of anti-idiotype binders. In this study, we evaluated the potential of generating patient-specific binders against the idiotype of lymphomas. To this end, the BCRs of three different lymphoma cell lines SUP-B8, Daudi, and IM-9 were identified, the variable domains were reformatted and the resulting monoclonal antibodies produced. The SUP-B8 BCR served as antigen in fluorescence-activated cell sorting (FACS)-based screening of the yeast-displayed vNAR libraries which resulted after three rounds of screening in the enrichment of antigen-binding vNARs. Five vNARs were expressed as Fc fusion proteins and consequently analyzed for their binding to soluble antigen using biolayer interferometry (BLI) revealing binding constants in the lower single-digit nanomolar range. These variants showed specific binding to the parental SUP-B8 cell line confirming a similar folding of the recombinantly expressed proteins compared with the native cell surface-presented BCR. First initial experiments to utilize the generated vNAR-Fc variants for BCR-clustering to induce apoptosis or ADCC/ADCP did not result in a significant decrease of cell viability. Here, we report an alternative approach for a personalized B-cell lymphoma therapy based on the construction of vNAR-Fc antibody-drug conjugates to enable specific killing of malignant B cells, which may widen the therapeutic window for B-cell lymphoma therapy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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  • 2
    In: EPJ Quantum Technology, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2021-12)
    Abstract: Microgravity eases several constraints limiting experiments with ultracold and condensed atoms on ground. It enables extended times of flight without suspension and eliminates the gravitational sag for trapped atoms. These advantages motivated numerous initiatives to adapt and operate experimental setups on microgravity platforms. We describe the design of the payload, motivations for design choices, and capabilities of the Bose-Einstein Condensate and Cold Atom Laboratory (BECCAL), a NASA-DLR collaboration. BECCAL builds on the heritage of previous devices operated in microgravity, features rubidium and potassium, multiple options for magnetic and optical trapping, different methods for coherent manipulation, and will offer new perspectives for experiments on quantum optics, atom optics, and atom interferometry in the unique microgravity environment on board the International Space Station.
    Type of Medium: Online Resource
    ISSN: 2662-4400 , 2196-0763
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2784501-1
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