Development of Chimeric Antigen Receptors Targeting Multiple Myeloma

我工作的一个重要重点是为多发性骨髓瘤开发嵌合抗原受体T细胞疗法，多发性骨髓瘤是一种通常无法治愈的浆细胞恶性肿瘤。多发性骨髓瘤表达CAR的T细胞疗法发展的一个主要障碍是缺乏合适的靶抗原。抗BCMA汽车：我最近设计和制造了两辆专门识别B细胞成熟抗原(BCMA)的汽车。BCMA在正常组织中的表达模式非常有限，但BCMA在多发性骨髓瘤的恶性浆细胞上表达。7我构建的BCMA特异性CARS在体外功能分析中特异性识别多发性骨髓瘤细胞系。抗BCMA Car表达的T细胞可根治小鼠骨髓瘤。应用免疫组织化学和定量聚合酶链式反应对BCMA在正常人体组织中的表达进行了广泛的分析。免疫组织化学显示，除正常浆细胞表达外，BCMA在正常人体器官中均未见表达。去年发表了一篇关于该项目的论文和摘要。抗BCMA-CAR转导的T细胞治疗晚期多发性骨髓瘤的临床试验正在计划中，临床级别的基因治疗试剂正在为这项临床试验准备。其他针对多发性骨髓瘤的CARS：除了开发抗BCMA的CARS外，我的目标是开发针对多发性骨髓瘤细胞表达的其他抗原的CARS，但不是正常的基本组织。一些有希望的候选抗原已经被确定，并开始对这些抗原进行初步评估。

An important focus of my work is development of chimeric antigen receptor T cell therapies for multiple myeloma, which is a usually incurable malignancy of plasma cells. A major obstacle to development of CAR-expressing T-cell therapies for multiple myeloma is the lack of suitable target antigens. Anti-BCMA CARs: I have recently designed and constructed two CARs that specifically recognize B-cell maturation antigen (BCMA). BCMA has a very restricted expression pattern in normal tissues, but BCMA is expressed on the malignant plasma cells of multiple myeloma.7 The BCMA specific CARs that I have constructed specifically recognize multiple myeloma cell lines in functional assays in vitro. Anti-BCMA CAR-expressing T cells can eradicate myeloma tumors in mice. An extensive analysis of BCMA expression in normal human tissues by immunohistochemistry and quantitative PCR has been conducted. Except for expression by normal plasma cells, BCMA expression was not detected in nomal human organs by immunohistochemistry. a paper and an abstract on this project have been published in the past year. A clinical trial of anti-BCMA-CAR-transduced T cells for treating advanced multiple myeloma is being planned, and clinical-grade gene therapy reagents are being prepared for this clinical trial. Other CARs targeting multiple myeloma: In addition to developing anti-BCMA CARs, I aim to develop CARs that target other antigens that are expressed by multiple myeloma cells but not normal essential tissues. Some promising candidate antigens have been identified, and initial evaluation of these antigens has begun.