Natural Killer Cells in the Malignant Niche of Multiple Myeloma.

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK cell function occurring in MM.

Focus on monoclonal antibodies targeting B-cell maturation antigen (BCMA) in multiple myeloma: update 2021.

Remarkable advances have been achieved in the treatment of multiple myeloma (MM) in the last decade, which saw targeted immunotherapy, represented by anti-CD38 monoclonal antibodies, successfully incorporated across indications. However, myeloma is still considered curable in only a small subset of patients, and the majority of them eventually relapse. B-cell maturation antigen (BCMA) is expressed exclusively in mature B lymphocytes and plasma cells, and represents an ideal new target for immunotherapy, presented by bispecific antibody (bsAb) constructs, antibody-drug conjugates (ADCs) and chimeric antigen receptor T (CAR-T) cells. Each of them has proved its efficacy with the potential for deep and long-lasting responses as a single agent therapy in heavily pretreated patients. As a result, belantamab mafodotin was approved by the United States Food and Drug Administration for the treatment of relapsed/refractory MM, as the first anti-BCMA agent. In the present review, we focus on monoclonal antibodies targeting BCMA - bsAbs and ADCs. The data from preclinical studies as well as first-in-human clinical trials will be reviewed, together with the coverage of their constructs and mechanisms of action. The present results have laid the groundwork for the ongoing or upcoming clinical trials with combinatory regimens, which have always been a cornerstone in the treatment of MM.

Fast-proliferating adipose tissue mesenchymal-stromal-like cells for therapy.

Human mesenchymal stromal cells, whether from the bone marrow or adipose tissue (hASCs), are promising cell therapy agents. However, generation of abundant cells for therapy remains to be a challenge, due to the need of lengthy expansion and the risk of accumulating genomic defects during the process. We show that hASCs can be easily induced to a reversible fast-proliferating phenotype (FP-ASCs) that allows rapid generation of a clinically useful quantity of cells in <2 weeks of culture. Expanded FP-ASCs retain their finite expansion capacity and pluripotent properties. Despite the high proliferation rate, FP-ASCs show genomic stability by array-comparative genomic hybridization, and did not generate tumors when implanted for a long time in an SCID mouse model. Comparative analysis of gene expression patterns revealed a set of genes that can be used to characterize FP-ASCs and distinguish them from hASCs. As potential candidate therapeutic agents, FP-ASCs displayed high vasculogenic capacity in Matrigel assays. Moreover, application of hASCs and FP-ASCs in a fibrin scaffold over a myocardium infarct model in SCID mice showed that both cell types can differentiate to endothelial and myocardium lineages, although FP-ASCs were more potent angiogenesis inducers than hASCs, at promoting myocardium revascularization.