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Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma

Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune...

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Autores principales: Sun, Jennifer, Muz, Barbara, Alhallak, Kinan, Markovic, Matea, Gurley, Shannon, Wang, Zhe, Guenthner, Nicole, Wasden, Katherine, Fiala, Mark, King, Justin, Kohnen, Daniel, Salama, Noha Nabil, Vij, Ravi, Azab, Abdel Kareem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072283/
https://www.ncbi.nlm.nih.gov/pubmed/32012878
http://dx.doi.org/10.3390/cancers12020305
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author Sun, Jennifer
Muz, Barbara
Alhallak, Kinan
Markovic, Matea
Gurley, Shannon
Wang, Zhe
Guenthner, Nicole
Wasden, Katherine
Fiala, Mark
King, Justin
Kohnen, Daniel
Salama, Noha Nabil
Vij, Ravi
Azab, Abdel Kareem
author_facet Sun, Jennifer
Muz, Barbara
Alhallak, Kinan
Markovic, Matea
Gurley, Shannon
Wang, Zhe
Guenthner, Nicole
Wasden, Katherine
Fiala, Mark
King, Justin
Kohnen, Daniel
Salama, Noha Nabil
Vij, Ravi
Azab, Abdel Kareem
author_sort Sun, Jennifer
collection PubMed
description Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the “don’t eat me” signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 “don’t eat me” signal is a novel and promising strategy for the treatment of MM, providing a basis for additional studies to validate these effects in vivo and in patients.
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spelling pubmed-70722832020-03-19 Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma Sun, Jennifer Muz, Barbara Alhallak, Kinan Markovic, Matea Gurley, Shannon Wang, Zhe Guenthner, Nicole Wasden, Katherine Fiala, Mark King, Justin Kohnen, Daniel Salama, Noha Nabil Vij, Ravi Azab, Abdel Kareem Cancers (Basel) Article Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the “don’t eat me” signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 “don’t eat me” signal is a novel and promising strategy for the treatment of MM, providing a basis for additional studies to validate these effects in vivo and in patients. MDPI 2020-01-28 /pmc/articles/PMC7072283/ /pubmed/32012878 http://dx.doi.org/10.3390/cancers12020305 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Jennifer
Muz, Barbara
Alhallak, Kinan
Markovic, Matea
Gurley, Shannon
Wang, Zhe
Guenthner, Nicole
Wasden, Katherine
Fiala, Mark
King, Justin
Kohnen, Daniel
Salama, Noha Nabil
Vij, Ravi
Azab, Abdel Kareem
Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma
title Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma
title_full Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma
title_fullStr Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma
title_full_unstemmed Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma
title_short Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma
title_sort targeting cd47 as a novel immunotherapy for multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072283/
https://www.ncbi.nlm.nih.gov/pubmed/32012878
http://dx.doi.org/10.3390/cancers12020305
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