CAR NK92 Cells Targeting BCMA Can Effectively Kill Multiple Myeloma Cells Both In Vitro and In Vivo.

Multiple myeloma (MM) is a hematological malignancy caused by malignant proliferation of plasma cells in bone marrow. Over the last decade, the survival outcome of patients with multiple myeloma (MM) has been substantially improved with the emergence of novel therapeutic agents. However, MM remains an incurable neoplastic plasma cell disorder. In addition, almost all MM patients inevitably relapse due to drug resistance. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. In this study, NK92 cells were engineered to express the third generation of BCMA CAR. In vitro, BCMA CAR-engineered NK92 cells displayed higher cytotoxicity and produced more cytokines such as IFN-γ and granzyme B than NK92 cells when they were co-cultured with MM cell lines. Furthermore, BCMA CAR-engineered NK92 cells released significantly higher amounts of cytokines and showed higher cytotoxicity when they were exposed to primary cells isolated from MM patients. The cytotoxicity of BCMA CAR NK92 cells was enhanced after MM cells were treated with bortezomib. Additionally, BCMA CAR NK92 cells exhibited potent antitumor activities in subcutaneous tumor models of MM. These results demonstrate that regional administration of BCMA CAR NK92 cells is a potentially promising strategy for treating MM.

Diagnostic and therapeutic biomarkers for Alzheimer's disease in human-derived platelets.

BACKGROUND: Diagnosis of current Alzheimer's disease (AD) is difficult even for medical specialists, and there is no clear biomarker. Also, aging is highly related to the onset of AD. OBJECTIVES: The purpose of this study is to screen miRNA as an aging-considered biomarker for AD treatment and diagnosis. METHODS: The patient group for this study was divided into a young normal, old normal, or AD group. We developed a method of discovering sequentially expressed miRNAs to distinguish miRNAs that were sequentially expressed in the three groups. RESULTS: Sequentially expressed miRNAs correlated highly with the patient's age, and most showed expression patterns that distinguished young, old, and AD. Specifically, the miRNA expression we found showed similar patterns in the brains of patients with AD. Among the selected miRNAs, one set derived from the same precursor: The expression of miR-150 was a disease- and age-specific downregulation in both 3p and 5p forms, and the precursor also had the same pattern. We named that triple matching. Also, the found miR-150 precursor had AD-specific miRNA-imbalance characteristics. CONCLUSIONS: We developed a novel AD diagnostic method using triple matching and miRNA-imbalance. The triple matching and miRNA imbalance-based relative ratio diagnosis method we developed will be very powerful in resolving the challenges of absolute diagnostic quantification based on biomarker expression. Also, our research results suggest the possibility of a treatment target for AD.