Engineering Circulating Tumor Cells as Novel Cancer Theranostics
Engineering Circulating Tumor Cells as Novel Cancer Theranostics
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DOI：
10.7150/thno.44259
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Ronald, John A.
中科院分区：
文献类型：
--
作者：
Parkins, Katie M.;Dubois, Veronica P.;Ronald, John A.
迫切需要靶向和治疗转移性疾病的新方法。肿瘤“自归巢”描述了循环肿瘤细胞（CTC）募集回到先前切除的原发性肿瘤位置，导致肿瘤复发，以及它们迁移到已建立的转移性病变。最近，自归巢CTC已被开发作为临床前原发性肿瘤模型中抗癌治疗剂的递送载体。然而，CTC自我归巢和治疗转移性疾病的能力在很大程度上是未知的。方法：在这里，我们使用生物发光成像（BLI）来探索全身给药的CTC是否归巢转移性病变，以及是否可以使用带有报告基因和细胞毒性前药基因疗法的CTC来可视化和治疗转移性疾病。结果：随着时间的推移进行的BLI显示了CTC在全身范围内归巢和治疗肿瘤的显着能力。令人兴奋的是，接受治疗性CTCs的小鼠中的转移性肿瘤负荷较低，接受对照CTCs.Conclusion的小鼠：这项研究表明，值得注意的能力，实验性CTCs的家庭播散性乳腺癌病变。此外，通过将前药基因治疗系统并入我们的自归巢CTC中，我们在有效和靶向递送基于基因的治疗剂以治疗原发性和转移性病变方面取得了令人兴奋的进展。
New ways to target and treat metastatic disease are urgently needed. Tumor "self-homing" describes the recruitment of circulating tumor cells (CTCs) back to a previously excised primary tumor location, contributing to tumor recurrence, as well as their migration to established metastatic lesions. Recently, self-homing CTCs have been exploited as delivery vehicles for anti-cancer therapeutics in preclinical primary tumor models. However, the ability of CTCs to self-home and treat metastatic disease is largely unknown.Methods: Here, we used bioluminescence imaging (BLI) to explore whether systemically administered CTCs home to metastatic lesions and if CTCs armed with both a reporter gene and a cytotoxic prodrug gene therapy can be used to visualize and treat metastatic disease.Results: BLI performed over time revealed a remarkable ability of CTCs to home to and treat tumors throughout the body. Excitingly, metastatic tumor burden in mice that received therapeutic CTCs was lower compared to mice receiving control CTCs.Conclusion: This study demonstrates the noteworthy ability of experimental CTCs to home to disseminated breast cancer lesions. Moreover, by incorporating a prodrug gene therapy system into our self-homing CTCs, we show exciting progress towards effective and targeted delivery of gene-based therapeutics to treat both primary and metastatic lesions.