Preclinical development of anti-BCMA immunotoxins targeting multiple myeloma Article Swipe
Zoë Shancer
,
M. Williams
,
Austin D. Igelman
,
Satoshi Nagata
,
Tomoko Ise
,
Ira Pastan
,
Tapan K. Bera
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1093/abt/tby004
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1093/abt/tby004
Background Multiple myeloma (MM) is a B-cell malignancy that is incurable for the majority of patients. New treatments are urgently needed. Recombinant immunotoxins (RITs) are chimeric proteins that are composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein and an ideal target for antibody-based treatments for MM. Methods RITs were produced by expressing plasmids encoding the components of the anti-BCMA RITs in Escherichia coli followed by inclusion body preparation, solubilization, renaturation, and purification by column chromatography. The cytotoxic activity of RITs was tested in vitro by WST-8 assays. We also measured their binding to human and mouse serum albumins and to BCMA and measured their serum half-life in mice. Results Using Fvs from different anti-BCMA antibodies, we produced RITs that specifically kill BCMA-expressing MM cells in vitro. To increase the serum half-life in vivo, we generated RITs that are fused with albumin-binding domains (ABDs). All RITs with ABDs have some decreased activity compared to the parent RIT, which is not due to decreased binding to BCMA. Conclusions Various new anti-BCMA immunotoxins were produced and evaluated. None of these were better than LMB-75 (anti-BCMA BM306-disulfide-stabilized Fv-LRggs) supporting the further preclinical development of LMB-75.
Related Topics
Concepts
Immunotoxin
Antibody
Molecular biology
In vitro
In vivo
Monoclonal antibody
Chemistry
Fusion protein
Recombinant DNA
Cytotoxicity
Biochemistry
Biology
Immunology
Gene
Biotechnology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/abt/tby004
- https://academic.oup.com/abt/article-pdf/1/1/19/34926952/tby004.pdf
- OA Status
- gold
- Cited By
- 9
- References
- 16
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2888327410
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2888327410Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/abt/tby004Digital Object Identifier
- Title
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Preclinical development of anti-BCMA immunotoxins targeting multiple myelomaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
-
2018-06-01Full publication date if available
- Authors
-
Zoë Shancer, M. Williams, Austin D. Igelman, Satoshi Nagata, Tomoko Ise, Ira Pastan, Tapan K. BeraList of authors in order
- Landing page
-
https://doi.org/10.1093/abt/tby004Publisher landing page
- PDF URL
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https://academic.oup.com/abt/article-pdf/1/1/19/34926952/tby004.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://academic.oup.com/abt/article-pdf/1/1/19/34926952/tby004.pdfDirect OA link when available
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Immunotoxin, Antibody, Molecular biology, In vitro, In vivo, Monoclonal antibody, Chemistry, Fusion protein, Recombinant DNA, Cytotoxicity, Biochemistry, Biology, Immunology, Gene, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2023: 1, 2022: 1, 2021: 1, 2020: 4, 2019: 2Per-year citation counts (last 5 years)
- References (count)
-
16Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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