← 返回

递送有效 CAR-T 免疫疗法对抗 3D 实体瘤球状体的微水凝胶注射剂

英文原题:Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids.

查看英文原题

Micro-hydrogel injectables that deliver effective CAR-T immunotherapy against 3D solid tumor spheroids.

PubMed 2022/07/26(内容时间) Transl Oncol Q2 · IF 4.9(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

嵌合抗原受体(CAR-)T 细胞正在彻底改变癌症治疗,这直接源于其在血液系统恶性肿瘤治疗中的临床影响。然而对于实体瘤,CAR-T 细胞疗效仍然有限,主要由于复杂的免疫抑制性肿瘤微环境、进入肿瘤细胞效率低下以及杀伤细胞持久性差。在这项体外研究中,研究了一种可注射的、基于明胶的微水凝胶系统,该系统能够封装并递送有效的 CAR-T 治疗。靶向 TAG-72 的 CAR-T 细胞封装在这些微凝胶中,7 天后仍具有高活力(> 87%),与在正常扩增条件下生长的细胞相当,并保留了 T 细胞表型和功能。从微凝胶中回收的 CAR-T 细胞在体外对人卵巢癌以及三维肿瘤球体上表现出强效的靶向细胞毒性,能够完全消除肿瘤细胞。基于明胶的微水凝胶有潜力作为载体系统,增强 CAR-T 免疫治疗对实体瘤的治疗。

展开英文摘要原文

Chimeric antigen receptor (CAR-) T cells are revolutionizing cancer treatment, as a direct result of their clinical impact on the treatment of hematological malignancies.

However for solid tumors, CAR-T cell therapeutic efficacy remains limited, primarily due to the complex immunosuppressive tumor microenvironment, inefficient access to tumor cells and poor persistence of the killer cells. In this in vitro study, an injectable, gelatin-based micro-hydrogel system that can encapsulate and deliver effective CAR-T therapy is investigated.

CAR-T cells targeting TAG-72, encapsulated in these microgels possessed high viability (> 87%) after 7 days, equivalent to those grown under normal expansion conditions, with retention of the T cell phenotype and functionality.

Microgel recovered CAR-T cells demonstrated potent on-target cytotoxicity against human ovarian cancer in vitro and on three-dimensional tumor spheroids, by completely eliminating tumor cells. The gelatin-based micro-hydrogels have the potential to serve as carrier systems to augment CAR-T immunotherapeutic treatment of solid tumors.

论文信息

作者
Suraiya AB、Evtimov VJ、Truong VX、Boyd RL、Forsythe JS、Boyd NR
第一作者单位
Department of Materials Science and Engineering, Monash Institute of Medical Engineering, Monash University, Clayton, Victoria 3800, Australia; Cartherics Pty, Ltd., Clayton, Victoria 3168, Australia.Australia
通讯作者单位
Cartherics Pty, Ltd., Clayton, Victoria 3168, Australia. Electronic address: nicholas.boyd@hudson.org.au.Australia
期刊
Translational oncology2022 Oct
原文标识
PubMed 35905640 · DOI 10.1016/j.tranon.2022.101477