肿瘤细胞治疗研究
英文原题：Leveraging gene therapy to achieve long-term continuous or controllable expression of biotherapeutics.
此外，我们利用外显子跳跃策略构建了可诱导版本，并在 AAV 注射后至少 36 周内实现了可重复的按需表达。
通过嵌合抗原受体（CAR-T）或双特异性分子将T细胞重定向至癌细胞是突破性技术；但CAR-T需个体化生产，双抗通常需持续输注。我们利用腺相关病毒（AAV）基因转移，开发现货型单次给药方案，使蛋白免疫治疗药物在血清中持续维持较长时间。研究在CD19阳性淋巴瘤异种移植模型中验证概念：单次静脉注射表达分泌型blinatumomab的AAV，可作为CD19 CAR-T治疗的通用替代方案。此外，利用外显子跳跃策略构建可诱导版本，在AAV注射后至少36周内实现按需重复表达。本系统亦可考虑用于非癌症适应证，以短期和/或重复表达其他目标转基因。
T cells redirected to cancer cells either via a chimeric antigen receptor (CAR-T) or a bispecific molecule have been breakthrough technologies; however, CAR-T cells require individualized manufacturing and bispecifics generally require continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics via adeno-associated virus (AAV) gene transfer. We demonstrate proof of principle in a CD19 + lymphoma xenograft model using a single intravenous dose of AAV expressing a secreted version of blinatumomab, which could serve as a universal alternative for CD19 CAR-T cell therapy. In addition, we created an inducible version using an exon skipping strategy and achieved repeated, on-demand expression up to at least 36 weeks after AAV injection. Our system could be considered for short-term and/or repeated expression of other transgenes of interest for noncancer applications.
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