Tumor-specific delivery of biologics by a novel T-cell line HOZOT.
Tumor-specific delivery of biologics by a novel T-cell line HOZOT.
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DOI：
10.1038/srep38060
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发表时间：
2016-11-30
影响因子：
4.6
通讯作者：
Fujiwara T
中科院分区：
文献类型：
--
作者：
Onishi T;Tazawa H;Hashimoto Y;Takeuchi M;Otani T;Nakamura S;Sakurai F;Mizuguchi H;Kishimoto H;Umeda Y;Shirakawa Y;Urata Y;Kagawa S;Fujiwara T
“细胞中细胞”表示一种侵入性表型，其中一种细胞主动内化于另一种细胞中。从人脐带血中建立的新型人T细胞系HOZOT被证明可以穿透各种人类癌细胞，但不能穿透正常细胞。溶瘤病毒正在成为人类癌症的生物疗法;然而，有效的病毒递送受到缺乏肿瘤特异性归巢和存在预先存在的或治疗诱导的中和抗体的限制。在这里，我们报告了一种新的，有趣的方法，使用HOZOT细胞通过细胞中细胞入侵将溶瘤病毒等生物制剂传输到人类癌细胞中。HOZOT细胞通过人CD 46抗原成功地负载了含有腺病毒血清型35（OBP-401/F35）的纤维蛋白的减毒腺病毒，其中端粒酶启动子调节病毒复制。负载OBP-401/F35的HOZOT细胞被有效地内化到人癌细胞中，并通过释放病毒表现出肿瘤特异性杀伤，即使在存在抗病毒中和抗体的情况下。此外，腹腔内施用负载有OBP-401/F35的HOZOT细胞显著抑制小鼠腹膜播散的肿瘤生长。这种独特的细胞中细胞特性为生物制剂选择性递送到人类癌细胞中提供了平台，这对人类癌症的治疗具有重要意义。
“Cell-in-cell” denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion. HOZOT cells were successfully loaded via human CD46 antigen with an attenuated adenovirus containing the fiber protein of adenovirus serotype 35 (OBP-401/F35), in which the telomerase promoter regulates viral replication. OBP-401/F35–loaded HOZOT cells were efficiently internalized into human cancer cells and exhibited tumor-specific killing by release of viruses, even in the presence of anti-viral neutralizing antibodies. Moreover, intraperitoneal administration of HOZOT cells loaded with OBP-401/F35 significantly suppressed peritoneally disseminated tumor growth in mice. This unique cell-in-cell property provides a platform for selective delivery of biologics into human cancer cells, which has important implications for the treatment of human cancers.
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通讯作者：
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