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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...

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Autores principales: Bannas, Peter, Koch-Nolte, Friedrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
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.
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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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