放化疗联合免疫治疗是目前缓解多发性骨髓瘤老年患者的主要手段。复发难治性多发性骨髓瘤患者，由于出现免疫耐受导致杀伤细胞的靶向性差，因此疗效欠佳。以嵌合抗原受体修饰T细胞的可有效提高体外输注免疫细胞对肿瘤细胞的识别和杀伤能力。CD138是骨髓瘤细胞表面较为特异的抗原标志。本项目将通过构建重组的 scFvCD138-CD8-CD137-CD3ζ嵌合受体基因并成功转染T细胞，建立嵌合抗原受体（Chimeric Antigen Receptor, CAR）工程化CD8/CD56双阳性T细胞实验体系，以期探索CART 138细胞在SCID鼠模型体内是否能长期、有效、特异的发挥抗肿瘤作用；并通过临床试验观察CART 138细胞对CD138+的复发难治性多发性骨髓瘤的疗效，解析其可能的机制。本项目的完成将建立起新一代CART细胞治疗技术，并为复发难治多发性骨髓瘤患者带来新的治疗希望。

At present, primary treatments of elderly patients with multiple myeloma were chemotherapy, immunotherapy with immunotherapy, but for relapsed and refractory patients, immune tolerance make the poor targeting of tumor cells and void therapeutic effect. T cells with the chimeric antigen receptors appear modifications may improve the capacity and identification of immune cells in vitro tumor cell killing. CD138 is a fairly specific surface antigen markers in myeloma cell, our study was to construct reorganization scFvCD138-CD8-CD137-CD3ζ chimeric receptor gene transfected T cells and establish CAR(Chimeric Antigen Receptor) engineered CD8/CD56 double positive T cells in experimental systems successfully in order to explore the CART 138 cells in SCID mouse model in vivo whether it have the long-term, effective and specific anti-tumor effect; the efficacy of CART 138 cells multiple myeloma will be observed by clinical trials, besides, further study should be done on its possibly mechanism. Based on these foundation, researches on new generation CART cell technology will be hopeful to bring new treatments for patients with relapsed and refractory multiple myeloma.