ArticleFrontiers in immunology2018
CD38-Specific Biparatopic Heavy Chain Antibodies Display Potent Complement-Dependent Cytotoxicity Against Multiple Myeloma Cells.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Camelid VHHs as a Versatile Platform for Combating Viral Infections.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Biparatopic targeting of CD38 using CD38-specific trimeric antibody recruiters improves cytotoxicity against multiple myeloma.Frontiers in immunology · 2026Article
- Article
- CD38-specific nanobody-based bispecific antibody recruiters (BARs) redirect complement-dependent cytotoxicity toward multiple myeloma cells.Scientific reports · 2025Article
- Review
- Leveraging Vγ9Vδ2 T cells against prostate cancer through a VHH-based PSMA-Vδ2 bispecific T cell engager.iScience · 2024Article
- Recent advances in targeted drug delivery systems for multiple myeloma.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- CD38 as theranostic target in oncology.Journal of translational medicine · 2024Review
- Establishment of an indirect competitive immunoassay for the detection of dicamba based on a highly specific nanobody.The Science of the total environment · 2024Article
- Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma.Nature communications · 2024Article
- Generation and characterization of antagonistic anti-human CD39 nanobodies.Frontiers in immunology · 2024Article
- Nanobody-based pannexin1 channel inhibitors reduce inflammation in acute liver injury.Journal of nanobiotechnology · 2023Article
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Half-Life Extended Nanobody-Based CD38-Specific Bispecific Killercell Engagers Induce Killing of Multiple Myeloma Cells.Frontiers in immunology · 2022Article
- Development of Antibody and Nanobody Tools for P2X7.Methods in molecular biology (Clifton, N.J.) · 2022Article
- CD38-specific nanobodies allowFrontiers in immunology · 2022Article
- Targeting multiple myeloma with nanobody-based heavy chain antibodies, bispecific killer cell engagers, chimeric antigen receptors, and nanobody-displaying AAV vectors.Frontiers in immunology · 2022Review
- Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.Frontiers in medicine · 2022Article
- Vaccinal antibodies: Fc antibody engineering to improve the antiviral antibody response and induce vaccine-like effects.Human vaccines & immunotherapeutics · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD38 is overexpressed by multiple myeloma cells and has emerged as a target for therapeutic antibodies. Nanobodies are soluble single domain antibody fragments derived from the VHH variable domain of heavy chain antibodies naturally occurring in camelids. We previously identified distinct llama nanobodies that recognize three non-overlapping epitopes of the extracellular domain of CD38. Here, we fused these VHH domains to the hinge, CH2, and CH3 domains of human IgG1, yielding highly soluble chimeric llama/human heavy chain antibodies (hcAbs). We analyzed the capacity of these hcAbs to mediate complement-dependent cytotoxicity (CDC) to CD38-expressing human multiple myeloma and Burkitt lymphoma cell lines. Combinations of two hcAbs that recognize distinct, non-overlapping epitopes of CD38 mediated potent CDC, in contrast to the hcAb monotherapy with only weak CDC capacity. Similarly, combining daratumumab with a hcAb that recognizes a non-overlapping epitope resulted in dramatically enhanced CDC. Further, introducing the E345R HexaBody mutation into the CH3 domain strongly enhanced the CDC potency of hcAbs to CD38-expressing cells. Exploiting their high solubility, we genetically fused two distinct nanobodies into heteromeric dimers via a flexible peptide linker and then fused these nanobody dimers to the hinge, CH2 and CH3 domains of human IgG1, yielding highly soluble, biparatopic hcAbs. These biparatopic hcAbs elicited CDC toward CD38-expressing myeloma cells more effectively than daratumumab. Our results underscore the advantage of nanobodies vs. pairs of VH and VL domains for constructing bispecific antibodies. Moreover, the CD38-specific biparatopic heavy chain antibodies described here represent potential new powerful therapeutics for treatment of multiple myeloma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.