Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.

Regulation of cell adhesion by heparan sulfate proteoglycan in adenomatoid odontogenic tumour

During recent years, attention was drawn to the role of cell adhesion in tumour development and progression. Cell-cell and cell-extracellular matrix interaction is crucial with regard to tumorous transformation and tumour spreading. There are numerous data indicating that the expression of syndecan-1 an important transmembrane proteoglycan undergoes changes during the development of several tumours. CD 138 antibody reacts with the core protein of syndecan-1, cell surface integral membrane heparin sulfate and chondroitin sulfate containing proteoglycan that binds to interstitial extracellular matrix molecules, thereby regulating cell adhesion. The predominant location of syndecan-1 is on epithelial cells where its expression correlates with normal epithelial organization. Previous studies have demonstrated that decreased expression of CD 138 is linked to malignant progression. Hitherto, few studies on the expression of CD138 in odontogenic tumours have been published and no studies have been found regarding the expression of this marker in adenomatoid odontogenic tumour [AOT]. Therefore, this study was carried out to highlight the recent concepts of cell adhesion in tumour development and progression in AOT using CD 138 monoclonal antibody. In respect to this, formalin-fixed, paraffinembedded tissue sections of 7 cases of AOT were selected in an attempt to clarify the peculiar histopathological features of this lesion. All studied cases showed positive reaction to the marker used, however differences were observed among the studied cases regarding areas of immunoreactivity and optical density of the positive areas. Overexpressions of CD138 were observed as cytoplasmic immunoreactivity especially in the spindle cells bordering the sheets and masses of the polyhedral cells and in the scanty stromal cells. The duct like structures and masses of polyhedral cells showed negative reactions. The results of the present study explain why AOT is a benign non-aggressive lesion