TY - JOUR
T1 - Targeting CD47 as a novel immunotherapy for multiple myeloma
AU - Sun, Jennifer
AU - Muz, Barbara
AU - Alhallak, Kinan
AU - Markovic, Matea
AU - Gurley, Shannon
AU - Wang, Zhe
AU - Guenthner, Nicole
AU - Wasden, Katherine
AU - Fiala, Mark
AU - King, Justin
AU - Kohnen, Daniel
AU - Salama, Noha Nabil
AU - Vij, Ravi
AU - Azab, Abdel Kareem
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - 3D tissue culture model
KW - Checkpoint inhibitors
KW - Macrophages
KW - Multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=85078862454&partnerID=8YFLogxK
U2 - 10.3390/cancers12020305
DO - 10.3390/cancers12020305
M3 - Article
C2 - 32012878
AN - SCOPUS:85078862454
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 2
M1 - 305
ER -