非霍奇金淋巴瘤（NHL）是发病率高、预后差的淋巴组织恶性肿瘤, 95%NHL细胞表达CD19和CD20抗原。本课题组前期联合抗CD3/抗CD19双特异抗体与ex4-1BBL/抗CD20融合蛋白治疗NHL取得了较好效果,但药物全身分布存在非特异激活全身免疫系统的风险。近年发现，脐带间充质干细胞（HUMSCs）能向肿瘤部位归巢，是理想的体内药物载体之一。因此，本研究经慢病毒整合上述两种蛋白药物基因到HUMSC基因组，利用HUMSC向肿瘤部位归巢并持续分泌表达外源基因的能力，实现了免疫活性药物在肿瘤微环境内的特异性、高浓度分布，使其介导的T细胞激活和CD19+CD20+细胞靶向杀伤仅仅局限于肿瘤局部，从而有效避免了正常细胞表面CD19、CD20抗原对靶向治疗的干扰及个体化差异导致的药物剂量依赖毒性。这一“双靶向”概念很好的体现了未来肿瘤多靶点治疗的理念，或成为NHL等肿瘤的新的临床治疗手段。

Non-hodgkin's lymphoma (NHL) is a high incidence of lymphoid tissue malignant tumor with poor prognosis and 95% NHL cells express CD19,CD20 antigen. Our previous research have proved that combination anti-CD3/anti-CD19 bispecific antibody with ex4-1 BBL/anti-CD20 fusion protein for NHL treatment has obtained the good effect, but exists the risk of the immune system nonspecific activation. In recent years,human umbilical cord mesenchymal stem cells (HUMSCs) was believed to be one of the ideal drug carriers with ability of homing tumor site.Therefore, this research integrated the above protein drugs gene to HUMSC genome by lenti virus and sustained expressing exogenous genes after HUMSC homing to the tumor site.We produced high concentration drugs which mediated T cell activation and CD19 + CD20 + cells targeted clear within the tumor microenvironment at the first time,which effectively avoid the interference of targeted therapy by normal cell surface CD19, CD20 antigen and drug dose dependent toxicity caused by individualized differences. This "double targeting" strategy conformed to the requirement of future multiple targets tumor therapy, or as a new clinical treatment of NHL and other tumors.