In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo.
In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo.
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用于体内循环T细胞中瞬时表达的体外转录抗原受体mRNA纳米载体。
DOI：
10.1038/s41467-020-19486-2
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发表时间：
2020-11-27
影响因子：
16.6
通讯作者：
Stephan MT
中科院分区：
文献类型：
--
作者：
Parayath NN;Stephan SB;Koehne AL;Nelson PS;Stephan MT
工程化嵌合抗原受体（CAR）或T细胞受体（TCR）有助于产生用于靶向治疗的疾病特异性T细胞，但与离体制造工程化T细胞相关的成本和严格性可能令人望而却步，因此体内编程T细胞可能是一种可行的替代方案。在这里，我们报告了一种可注射的纳米载体，其递送体外转录（IVT）CAR或TCR mRNA，用于循环T细胞的瞬时重编程以识别疾病相关抗原。在人白血病、前列腺癌和乙型肝炎诱导的肝细胞癌的小鼠模型中，这些聚合物纳米载体的重复输注诱导足够的表达肿瘤特异性汽车或病毒特异性TCR的宿主T细胞，从而以与离体工程化淋巴细胞的推注相似的水平引起疾病消退。鉴于其易于制造，分销和管理，这些纳米载体及其相关平台可能成为广泛疾病的治疗方法。抗原特异性T细胞的离体工程化已显示出治疗功效，但可能是昂贵且稀缺的。在这里，作者表明，包装在纳米载体中的体外转录的抗原受体mRNA可以直接诱导，在体内，在循环T细胞中瞬时表达，以在癌症或病毒感染的小鼠模型中提供治疗效果。
Engineering chimeric antigen receptors (CAR) or T cell receptors (TCR) helps create disease-specific T cells for targeted therapy, but the cost and rigor associated with manufacturing engineered T cells ex vivo can be prohibitive, so programing T cells in vivo may be a viable alternative. Here we report an injectable nanocarrier that delivers in vitro-transcribed (IVT) CAR or TCR mRNA for transiently reprograming of circulating T cells to recognize disease-relevant antigens. In mouse models of human leukemia, prostate cancer and hepatitis B-induced hepatocellular carcinoma, repeated infusions of these polymer nanocarriers induce sufficient host T cells expressing tumor-specific CARs or virus-specific TCRs to cause disease regression at levels similar to bolus infusions of ex vivo engineered lymphocytes. Given their ease of manufacturing, distribution and administration, these nanocarriers, and the associated platforms, could become a therapeutic for a wide range of diseases. Ex vivo engineering of antigen-specific T cells has shown therapeutic efficacy but can be costly and scarce. Here the authors show that in vitro-transcribed antigen receptor mRNA packaged in nanocarriers can directly induce, in vivo, transient their expression in circulating T cells to provide therapeutic effects in mouse models of cancer or viral infection.
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
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通讯作者：
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