首个转座子TCR-T将进入临床

首个非病毒载体TCR-T（转座子CAR-T已经进入临床：NCT00968760、NCT01497184、 NCT01362452、 NCT01653717和 NCT02194374等）

下面是流程图：转座子系统中，表达质粒的转座酶识别供体质粒上的末端反向重复序列后可以将包含TCR基因的完整转座子形式整合到染色体 DNA 中，也是整合到基因组，可以使目的基因的表达长期有效。

睡美人（SB）或者PiggyBaac转座子的制备和质控价格低于病毒载体，虽然也有随机插入致癌或破坏其他基因功能的风险，但是远低于病毒载体。此外还有个缺点就是基因转染效率较低且需要足够时间生产出足够数量的应用于治疗的细胞。

Ziopharm也提到成本这一点

特附几种病毒载体与转座子的比较如下

Ziopharm的SB TCR-T来自NCI的Steven Rosenberg，最早的文章

2016年他的团队就用睡美人转座子系统结合电转开发出高效的、成本控制的制备TCR-T的方法，并且验证了制备的TCR-T细胞特异性的针对抗原和肿瘤细胞的免疫功能

近期的文章，有兴趣可以看下，都是热点突变的新生抗原靶点

新闻原文

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BOSTON, June 11, 2019 (GLOBE NEWSWIRE) -- Ziopharm Oncology, Inc. (“Ziopharm” or “the Company”) (Nasdaq:ZIOP) announced that the investigational new drug (IND) application submitted by the National Cancer Institute (NCI) has received clearance from the U.S. Food and Drug Administration (FDA) for a clinical trial in solid tumors to evaluate T-cell receptor (TCR) T-cell therapy utilizing Ziopharm’s Sleeping Beauty platform.

“This study is the result of extensive work by Dr. Steven Rosenberg and his team at the NCI, including Dr. Drew Deniger, to harness our Sleeping Beauty non-viral gene transfer technology to express neoantigen-specific T-cell receptors (TCRs),” said Dr. Laurence Cooper, Chief Executive Officer of Ziopharm. “This important regulatory milestone combined with our recent license from the NCI for a library of TCRs reactive to mutations, or neoantigens, within KRAS, p53 and EGFR hotspots for use with the Sleeping Beauty platform, underscores the broad scope and potential of our TCR-T program. In collaboration with the NCI, we are now in position to be the first company to bring non-viral TCR-T into the clinic.”

Ziopharm and the NCI are partnered in a cooperative research and development agreement (CRADA), under the direction of Dr. Rosenberg, Chief of the Surgery Branch of the NCI, supporting clinical work to evaluate a non-viral approach to manufacturing TCR-T with the Sleeping Beauty platform that target solid tumors. With this approach, T cells can be genetically modified to express multiple, tumor-specific TCRs, which Ziopharm believes will be foundational technology to successfully targeting and treating metastatic solid tumors.