![]() Moreover, CD38 is expressed at high levels in a subset of B regulatory (Bregs) CD19 +CD24 hi cells and on IL-10-producing plasmablast with regulatory functions, on the other hand memory B cell population show a low expression of CD38 (CD24 hiCD38 loCD27 +) ( 25). It is present at high levels on BM B cell precursors (immature or transitional) and is downregulated in mature B cells and is expressed at high level in terminally differentiated PC ( 19). Subsequentially, CD38 expression is also modified during different stages of B cell differentiation. CD38 is also expressed at high levels by peripheral blood mononuclear cells upon in vitro and in vivo activation ( 24). Among CD8 T cells, CD38 is strongly expressed during chronic infection. ![]() CD38 is also a marker of activated T cells ( 19). Within the circulating pool, CD38 is expressed by CD4 +/CD45RA + naive T cells as well as by subset of CD4 +CD25 +FoxP3 + regulatory T cells (Tregs) and by a subset of memory T cells ( 19, 23). Moreover, CD38 is expressed by different T cells subtypes T cell precursors as CD4 +CD8 + double‐positive thymocytes ( 19). Resting natural killer (NKs) cells and monocytes express it at low levels, as well as other cell types belonging to the hematopoietic lineage ( Table 1): erythrocytes, platelets, and dendritic cells (DCs) ( 16, 20– 22). ![]() This molecule is widely expressed in lymphoid and myeloid lineages ( 14, 17– 19). Physiological Expression and Function of CD38 This review will describe main therapeutic targets in MM cells and the BM microenvironment and the mAbs in use in the anti-MM therapy focusing on their mechanism of actions and strategies to improve their efficacy. Several extensive and updated reviews are available about this topic ( 12, 13). The effector potential strength of the interaction between IgG mAbs and Fc engaging molecules will not be described, being out of scope of this manuscript. The IgG subclass, allotype, and glycosylation pattern are the main factors involved in the interaction strength of the IgG-Fc domain with Fc engaging molecules, including the classical IgG-Fc receptors (FcγR), the neonatal Fc-receptor (FcRn), the Tripartite motif-containing protein 21 (TRIM21), the first component of the classical complement cascade (C1), the Fc-receptor-like receptors (FcRL4/5). Isotype dictates mAbs activity ( 11), and most anti-MM mAbs are IgG antibodies. ![]() Moreover, the development of a new generation of mAbs, including antibody-drug conjugates (ADCs) and bispecific antibodies (bsAbs) has the potential to additional improve the clinical outcome of MM patients ( 6, 10). Monoclonal antibodies (mAbs) are a group of agents with immune-based mechanism of actions that in recent years have changed the management of newly diagnosed and relapsed/refractory MM (RRMM) ( 6, 9). Some of these molecules, such as Cluster of Differentiation 38 (CD38), signaling lymphocyte activation molecule family member 7 (SLAMF7), and B cell maturation antigen (BCMA), are highly expressed by MM PCs characterizing them as good target for novel therapeutic strategies as monoclonal antibodies ( 6– 8). MM PCs are strictly dependent on BM microenvironment cells and they express different molecules on the surface as receptors and adhesion molecules that exploit the function of crosstalk and adhesion with the BM microenvironment ( 5). However, thanks to increasing body of evidence about the molecular arms of MM/TME interaction and the introduction of multiple novel agents ( 3), median patient survival prolonged from 3 to 8–10 years ( 4). The cross talk between MM cells and their surrounding TME has been a major obstacle for the development of immunotherapy. Multiple Myeloma (MM) is the second most frequent hematological neoplasm, due to uncontrolled proliferation of neoplastic plasma cells (PCs) in and out the bone marrow (BM), surrounded by a permissive and protective tumor microenvironment (TME) ( 1, 2). ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |