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Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma
The NAD(+)-metabolizing ectoenzyme CD38 is an established therapeutic target in multiple myeloma. The CD38-specific monoclonal antibodies daratumumab and isatuximab show promising results in the clinic. Nanobodies correspond to the single variable domains (VHH) derived from heavy chain antibodies th...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232533/ https://www.ncbi.nlm.nih.gov/pubmed/30459772 http://dx.doi.org/10.3389/fimmu.2018.02559 |
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author | Bannas, Peter Koch-Nolte, Friedrich |
author_facet | Bannas, Peter Koch-Nolte, Friedrich |
author_sort | Bannas, Peter |
collection | PubMed |
description | The NAD(+)-metabolizing ectoenzyme CD38 is an established therapeutic target in multiple myeloma. The CD38-specific monoclonal antibodies daratumumab and isatuximab show promising results in the clinic. Nanobodies correspond to the single variable domains (VHH) derived from heavy chain antibodies that naturally occur in camelids. VHHs display high solubility and excellent tissue penetration in vivo. We recently generated a panel of CD38-specific nanobodies, some of which block or enhance the enzymatic activity of CD38. Fusion of such a nanobody to the hinge, CH2, and CH3 domains of human IgG1 generates a chimeric llama/human hcAb of about half the size of a conventional moAb (75 vs. 150 kDa). Similarly, a fully human CD38-specific hcAb can be generated using a CD38-specific human VH3 instead of a CD38-specific camelid nanobody. Here we discuss the advantages and disadvantages of CD38-specific hcAbs vs. conventional moAbs and provide an outlook for the potential use of CD38-specific hcAbs as novel therapeutics for multiple myeloma. |
format | Online Article Text |
id | pubmed-6232533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62325332018-11-20 Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma Bannas, Peter Koch-Nolte, Friedrich Front Immunol Immunology The NAD(+)-metabolizing ectoenzyme CD38 is an established therapeutic target in multiple myeloma. The CD38-specific monoclonal antibodies daratumumab and isatuximab show promising results in the clinic. Nanobodies correspond to the single variable domains (VHH) derived from heavy chain antibodies that naturally occur in camelids. VHHs display high solubility and excellent tissue penetration in vivo. We recently generated a panel of CD38-specific nanobodies, some of which block or enhance the enzymatic activity of CD38. Fusion of such a nanobody to the hinge, CH2, and CH3 domains of human IgG1 generates a chimeric llama/human hcAb of about half the size of a conventional moAb (75 vs. 150 kDa). Similarly, a fully human CD38-specific hcAb can be generated using a CD38-specific human VH3 instead of a CD38-specific camelid nanobody. Here we discuss the advantages and disadvantages of CD38-specific hcAbs vs. conventional moAbs and provide an outlook for the potential use of CD38-specific hcAbs as novel therapeutics for multiple myeloma. Frontiers Media S.A. 2018-11-06 /pmc/articles/PMC6232533/ /pubmed/30459772 http://dx.doi.org/10.3389/fimmu.2018.02559 Text en Copyright © 2018 Bannas and Koch-Nolte. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Bannas, Peter Koch-Nolte, Friedrich Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma |
title | Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma |
title_full | Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma |
title_fullStr | Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma |
title_full_unstemmed | Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma |
title_short | Perspectives for the Development of CD38-Specific Heavy Chain Antibodies as Therapeutics for Multiple Myeloma |
title_sort | perspectives for the development of cd38-specific heavy chain antibodies as therapeutics for multiple myeloma |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232533/ https://www.ncbi.nlm.nih.gov/pubmed/30459772 http://dx.doi.org/10.3389/fimmu.2018.02559 |
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