1. Targeting multiple myeloma with nanobody-based heavy chain antibodies, bispecific killer cell engagers, chimeric antigen receptors, and nanobody-displaying AAV vectors.
- Author
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Hambach J, Mann AM, Bannas P, and Koch-Nolte F
- Subjects
- Humans, ADP-ribosyl Cyclase 1, Immunoglobulin Heavy Chains therapeutic use, Killer Cells, Natural, Receptors, Chimeric Antigen genetics, Receptors, Chimeric Antigen therapeutic use, Multiple Myeloma drug therapy, Antibodies, Bispecific therapeutic use, Single-Domain Antibodies
- Abstract
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., Competing Interests: PB and FK-N are co-inventors on a patent application on CD38-specific nanobodies. AM and FK-N are co-inventors on a patent application on nanobody-displaying AAV vectors. FK-N receives a share of antibody and protein sales via MediGate GmbH, a wholly owned subsidiary of the University Medical Center Hamburg-Eppendorf. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. MediGate GmbH was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2022 Hambach, Mann, Bannas and Koch-Nolte.)
- Published
- 2022
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