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Anti-BCMA Immunotoxins: Design, Production, and Preclinical Evaluation.
- Source :
-
Biomolecules [Biomolecules] 2020 Sep 29; Vol. 10 (10). Date of Electronic Publication: 2020 Sep 29. - Publication Year :
- 2020
-
Abstract
- Multiple myeloma (MM) is a B-cell malignancy that is incurable for a majority of patients. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein highly expressed in multiple myeloma cells but not in other normal tissues except normal plasma B cells. Due to the restricted expression and being a cell surface membrane protein, BCMA is an ideal target for immunotherapy approaches in MM. Recombinant immunotoxins (RITs) are a novel class of protein therapeutics that are composed of the Fv or Fab portion of an antibody fused to a cytotoxic agent. RITs were produced by expressing plasmids encoding the components of the anti-BCMA RITs in E. 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 using BCMA expressing cell lines and on cells isolated from MM patients. The in vivo efficacy of RITs was tested in a xenograft mouse model using BCMA expressing multiple myeloma cell lines. Anti-BCMA recombinant immunotoxins are very effective in killing myeloma cell lines and cells isolated from myeloma patients expressing BCMA. Two mouse models of myeloma showed that the anti-BCMA immunotoxins can produce a long-term complete response and warrant further preclinical development.
- Subjects :
- Animals
B-Cell Maturation Antigen immunology
Gene Expression Regulation, Neoplastic drug effects
Humans
Immunoglobulin Variable Region immunology
Immunoglobulin Variable Region therapeutic use
Immunotoxins immunology
Mice
Multiple Myeloma genetics
Multiple Myeloma immunology
Multiple Myeloma pathology
Recombinant Proteins immunology
Recombinant Proteins therapeutic use
Xenograft Model Antitumor Assays
B-Cell Maturation Antigen therapeutic use
Cell Proliferation drug effects
Immunotoxins therapeutic use
Multiple Myeloma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 33003418
- Full Text :
- https://doi.org/10.3390/biom10101387