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Targeting multiple myeloma with nanobody-based heavy chain antibodies, bispecific killer cell engagers, chimeric antigen receptors, and nanobody-displaying AAV vectors

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1005800

Keywords

nanobody; multiple myeloma; CAR; heavy chain antibodies; BiKE; AAV; VHH; CD38

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Funding

  1. Deutsche Forschungsgemeinschaft [BA 5893/7, SFB1328-Z02]

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This article discusses the specificity and effectiveness of nanobody-based constructs in targeting CD38-expressing myeloma cells. Promising results have been obtained in preclinical studies, warranting further clinical research to evaluate the potential of these CD38-specific nanobody-based constructs for the treatment of multiple myeloma.
Nanobodies are well suited for constructing biologics due to their high solubility. We generated nanobodies directed against CD38, a tumor marker that is overexpressed by multiple myeloma and other hematological malignancies. We then used these CD38-specific nanobodies to construct heavy chain antibodies, bispecific killer cell engagers (BiKEs), chimeric antigen receptor (CAR)-NK cells, and nanobody-displaying AAV vectors. Here we review the utility of these nanobody-based constructs to specifically and effectively target CD38-expressing myeloma cells. The promising results of our preclinical studies warrant further clinical studies to evaluate the potential of these CD38-specific nanobody-based constructs for treatment of multiple myeloma.

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