Abstract
ABSTRACTTreatment for multiple myeloma (MM) has significantly advanced in the last decade with the introduction of proteasome inhibitors and immunomodulatory therapies. Unfortunately, MM continues to cause significant morbidity and most patients eventually succumb to the disease. As in other areas of cancer, immunotherapy in MM has also evolved and holds promise to deliver long-lasting remissions or even cure. The signaling lymphocyte activation molecules (SLAM) family of surface proteins represents a group of potential targets for immunotherapy in MM as some of the family members are expressed consistently on plasma cells and also on myeloma propagating pre-plasma cells. Here, we review the SLAM family members in detail, describe their tissue distribution, biologic pathways, as well as relevant pre-clinical studies and clinical trials in MM. Our review demonstrates the value of SLAM family receptors as potential targets for anti-myeloma immunotherapies and outlines how immunotherapeutic approaches can be developed.
Highlights
Clonal plasma cell dyscrasias represent a continuum of disorders from monoclonal gammopathy of unknown significance (MGUS) through smoldering myeloma (SMM) to multiple myeloma (MM) and plasma cell leukemia
Signaling lymphocyte activation molecule (SLAM) family receptors are expressed on the surface of different immune cells, they function as activating and inhibitory signal transducers, and they can potentially be used as targets for novel immunotherapies for MM and other lymphoid malignancies
We showed that CD229 is expressed on the CD19¡CD138¡ population of myeloma cells, which can be regarded as the myeloma-propagating pre-plasma cells that contributes to relapse and refractory disease.[24,25]
Summary
Clonal plasma cell dyscrasias represent a continuum of disorders from monoclonal gammopathy of unknown significance (MGUS) through smoldering myeloma (SMM) to multiple myeloma (MM) and plasma cell leukemia. The signaling lymphocyte activation molecules (SLAM) family of surface proteins represents a group of potential targets for immunotherapy in MM as some of the family members are expressed consistently on plasma cells and on myeloma propagating pre-plasma cells.
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