Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy.

Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy.
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实体瘤中汽车T细胞的散射播种增强了抗癌功效。

DOI:
10.1093/nsr/nwab172
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发表时间:
2022-03
影响因子:
20.6
通讯作者:
Gu Z
Gu Z
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li H;Wang Z;Ogunnaike EA;Wu Q;Chen G;Hu Q;Ci T;Chen Z;Wang J;Wen D;Du H;Jiang J;Sun J;Zhang X;Dotti G;Gu Z

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嵌合抗原受体T细胞(CAR T)治疗是治疗复发和难治性B细胞恶性肿瘤的一个里程碑。然而,CAR T细胞在实体瘤中的有益作用尚未获得。在这里,我们实施了一种容纳CAR T细胞的多孔微针贴片,当CAR T细胞被植入肿瘤床或手术后切除腔时,它允许CAR T细胞的原位穿透介导性种植。装载在微针尖端毛孔中的CAR T细胞很容易以均匀分散的方式被护送到肿瘤部位,而不会失去它们的活性。与直接瘤内注射相比,这种微针介导的局部给药增强了CAR T细胞的渗透和免疫刺激作用。这种可裁剪的贴片为分散种植活细胞提供了一个变革性的平台,用于治疗各种肿瘤。设计了一种多孔微针贴片来装载CAR T细胞,从而容易地将CAR T细胞护送到实体肿瘤,以均匀分散的方式打破物理屏障,而不会失去细胞的活性。
Chimeric antigen receptor T cell (CAR T) therapy was a milestone in the treatment of relapsed and refractory B cell malignancies. However, beneficial effects of CAR T cells have not been obtained in solid tumors yet. Herein, we implement a porous microneedle patch that accommodates CAR T cells and allows in situ penetration-mediated seeding of CAR T cells when implanted in the tumor bed or in the post-surgical resection cavity. CAR T cells loaded in the pores of the microneedle tips were readily escorted to the tumor in an evenly scattered manner without losing their activity. Such microneedle-mediated local delivery enhanced infiltration and immunostimulation of CAR T cells as compared to direct intratumoral injection. This tailorable patch offers a transformative platform for scattered seeding of living cells for treating a variety of tumors. A porous microneedle patch was elaborated to load CAR T cells, and thus readily escorted CAR T cells to the solid tumor to break the physical barrier in an evenly scattered manner without losing the cells’ activity.
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