Viral-based chimeric antigen receptor-engineered T (CAR T)–cell manufacturing has potential safety risks and relatively high costs. The nonviral minicircle DNA (mcDNA) is safer for patients, cheaper to produce, and may be a more suitable technique to generate CAR T cells. In this study, we produced mcDNA-based CAR T cells specifically targeting prostate stem cell antigen (PSCA; mcDNA-PSCA-CAR T cells). Our results showed that mcDNA-PSCA-CAR T cells persisted in mouse peripheral blood as long as 28 days and demonstrated more CAR T-cell infiltration, higher cytokine secretion levels, and better antitumor effects. Together, our results suggest that mcDNA-CAR can be a safe and cost-effective platform to produce CAR T cells.

中文翻译：

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Minicircle DNA 工程化 CAR T 细胞抑制小鼠肿瘤生长

基于病毒的嵌合抗原受体工程T（CAR T）-细胞制造具有潜在的安全风险和相对较高的成本。非病毒小环 DNA (mcDNA) 对患者来说更安全，生产成本更低，并且可能是更适合生成 CAR T 细胞的技术。在这项研究中，我们生产了基于 mcDNA 的 CAR T 细胞，专门针对前列腺干细胞抗原（PSCA；mcDNA-PSCA-CAR T 细胞）。我们的结果表明，mcDNA-PSCA-CAR T 细胞在小鼠外周血中持续存在长达 28 天，并表现出更多的 CAR T 细胞浸润、更高的细胞因子分泌水平和更好的抗肿瘤作用。总之，我们的结果表明 mcDNA-CAR 可以成为生产 CAR T 细胞的安全且具有成本效益的平台。