Injectable Porous Microchips with Oxygen Reservoirs and an Immune-Niche Enhance the Efficacy of CAR T Cell Therapy in Solid Tumors
Injectable Porous Microchips with Oxygen Reservoirs and an Immune-Niche Enhance the Efficacy of CAR T Cell Therapy in Solid Tumors
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具有储氧层和免疫生态位的可注射多孔微芯片增强 CAR T 细胞治疗实体瘤的疗效
DOI：
10.1021/acsami.0c15239
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发表时间：
2020-12-23
影响因子：
9.5
通讯作者：
Wei, Shicheng
中科院分区：
文献类型：
--
作者：
Luo, Zuyuan;Liu, Zhen;Wei, Shicheng
嵌合抗原受体(CAR)T细胞治疗是一种很有前途的新型血液系统恶性肿瘤治疗方法。然而，CAR T细胞在实体瘤治疗中很少有效，主要是由于注射的CAR T细胞向肿瘤部位的转运不佳，以及它们在免疫抑制和低氧肿瘤微环境(TME)中的有限浸润和存活。在这里，我们建立了一种可注射免疫微芯片(I-G/MC)系统，用于瘤内传递CAR T细胞，并增强其对实体瘤的治疗效果。在I-G/MC中，氧载体(Hemo)被释放以破坏TME，然后CART细胞从携带IL-I5的I-G/MC迁移到肿瘤间质。结果表明，HEMO和IL-15协同促进CAR T细胞在低氧条件下的存活和扩增，增强CAR T细胞的功能和记忆能力。这种I-G/MC不仅作为细胞载体，而且还建立了一个免疫利基，增强了CAR T细胞的效力。
Chimeric antigen receptor (CAR) T cell therapy is a promising new class of hematological malignancy treatment. However, CAR T cells are rarely effective in solid tumor therapy mainly because of the poor trafficking of injected CAR T cells to the tumor site and their limited infiltration and survival in the immunosuppressive and hypoxic tumor microenvironment (TME). Here, we built an injectable immune-microchip (i-G/MC) system to intratumorally deliver CAR T cells and enhance their therapeutic efficacy in solid tumors. In the i-G/MC, oxygen carriers (Hemo) are released to disrupt the TME, and then, CART cells migrate from IL-I5-laden i-G/MCs into the tumor stroma. The results indicate that Hemo and IL-15 synergistically enhanced CAR T cell survival and expansion under hypoxic conditions, promoting the potency and memory of CAR T cells. This i-G/MC not only serves as a cell carrier but also builds an immune-niche, enhancing the efficacy of CAR T cells.