Concomitant Use of CD138- and CD19-directed Chimeric Antigen Receptor-modified T Cells Enhances Cytotoxicity Towards Multiple Myeloma

Abstract

Multiple myeloma (MM) is a malignancy characterized by abnormal proliferation of clonal plasma cells, and it is the second most common hematologic malignancy in the world after non-Hodgkin lymphoma. In recent years, significant progress has been made in the clinical treatment of MM. In particular, certain novel drugs, such as bortezomib, lenalidomide, and carfilzomib, have greatly improved the survival rate of patients with MM. However, because of drug resistance, most MM patients eventually suffer a relapse and die of the disease. In this study, the chimeric antigen receptor-modified T cell (CAR-T cell) technology, which has achieved success in recent clinical trials for B-cell acute lymphoblastic leukemia (B-ALL), was used. In view of the high CD138 expression in MM cells and the presence of the CD138–/CD19+ phenotype in a small subset of MM cells, and based on preliminary findings of effective killing of MM cells by CD19-CAR-T cells in clinical studies, CD138- and CD19-directed CAR-T cells were constructed. Through in vitro experiments and the use of a mouse model, we proved that these two types of CAR-T cells possess strong biological activity in the specific killing of target cells, and that the concomitant use of these cells significantly enhances the killing effect in an MM mouse model.