TY - JOUR
T1 - Novel Insights in Anti-CD38 Therapy Based on CD38-Receptor Expression and Function: the Multiple Myeloma Model
AU - Zannetti, Beatrice Anna
AU - Faini, Angelo Corso
AU - Massari, Evita
AU - Geuna, Massimo
AU - Maffini, Enrico
AU - Poletti, Giovanni
AU - Cerchione, Claudio
AU - Martinelli, Giovanni
AU - Malavasi, Fabio
AU - Lanza, Francesco
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/12/11
Y1 - 2020/12/11
N2 - Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.
AB - Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.
KW - anti-CD38 monoclonal antibodies
KW - bone marrow microenvironment
KW - CD38
KW - CD38 antigen expression in various tissues
KW - multiple myeloma
KW - plasmacells
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U2 - 10.3390/cells9122666
DO - 10.3390/cells9122666
M3 - Article
C2 - 33322499
AN - SCOPUS:85098533003
VL - 9
JO - Cells
JF - Cells
SN - 2073-4409
IS - 12
ER -