人工APCs刺激T细胞对CD19-CD20-CAR在B淋巴细胞瘤治疗效果的研究

The preparation of chimeric antigen receptor T cells (CAR-T) is limited by low ex vivo expansion rate and weak functionality activation. Artificial antigen presenting cells (aAPCs) interact with primary T cells can improve the T cells proliferation rate and exhibit stronger functions of T cells. However, there are rarely reports on using microfluidic chip to mimic aAPCs. Exciting outcomes were obtained in single specific CAR-T therapy on B cell lymphoma, but some patients still relapsed after CD19-targeted CAR-T therapy. Moreover, using bispecific CAR-T effects on B cell lymphoma treatment need to be further investigated..This research will establish microfluidic chip and optimize the T cell culture conditions to provide the aAPCs environment for T cells expansion and activation. Using the functionality T cells activated by aAPCs to construct the bispecific CD19-CD20-CAR-T cells, and study the CAR-T cells therapeutic effects on lymphoma from cells and in vivo. This research will enhance the T cells proliferation rate in vitro and activated efficiency, shorten the preparation time of CAR-T cells, and elucidate the therapeutic efficacy of different functionality bispecific CD19-CD20-CAR-T on B cell lymphoma. More importantly, this will provide a more efficiency way for CAR-T cells preparation, and a more effective B cell lymphoma immunotherapy treatment.

制备嵌合抗原受体T细胞过程中，T细胞体外增殖缓慢和低活性是影响肿瘤免疫治疗周期的重要因素。人工模拟抗原递呈细胞环境能够提高相互作用的T细胞增殖速度和更强的功能，但利用微流控芯片制备aAPCs的研究却鲜有报道。单一靶向性的CAR-T对B细胞淋巴瘤治疗已呈现出显著疗效，但仍有患者出现复发情况，而串联性CAR-T对B细胞淋巴瘤治疗效果仍有待进一步研究。.本项目拟通过制备微流控芯片和优化芯片内T细胞培养环境，为T细胞增殖与激活提供aAPCs环境；并利用aAPCs激活的T细胞构建靶向特异性的串联CD19-CD20-CAR-T细胞，从体内外层面探讨CAR-T细胞对B细胞淋巴瘤的治疗效果。本项目将有助于提高T细胞体外增殖和激活效率，缩短CAR-T细胞制备周期，并阐明不同状态的串联CAR-T细胞对B细胞淋巴瘤治疗作用，为CAR-T细胞的制备提供更高效的方法以及更有效的B细胞淋巴瘤免疫治疗思路。