腹膜定向嵌合溶瘤病毒CF17预防恶性腹水并提高癌症腹膜转移的存活率。

IF 5.3 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Therapy Oncolytics Pub Date : 2023-10-19 eCollection Date: 2023-12-19 DOI:10.1016/j.omto.2023.100734
Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Jianming Lu, Sang-In Kim, Hannah Valencia, Yuman Fong, Yanghee Woo
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引用次数: 0

摘要

癌症腹膜转移(PM)在没有有效治疗的情况下是致命的。我们研究了CF17,一种新的具有复制能力的嵌合痘病毒,在体外对抗GC细胞系,并在攻击性GCPM小鼠模型中对抗PM。CF17处理后,我们对肠型和弥漫型人GC细胞系进行了病毒增殖和细胞毒性测定。在0.01、0.1的较低MOI下,大多数细胞系的杀伤率>80%,而在更具攻击性的细胞系中,在1.0和10.0的较高MOI下可观察到杀伤。我们在植入耐药GC细胞系的裸鼠中观察到腹膜内(i.p.)CF17治疗降低了腹膜肿瘤负荷并延长了生存期。在治疗后的第91天,CF17治疗组的八只小鼠中有七只存活,而对照组的八两只小鼠中有一只存活。CF17治疗抑制腹水形成(0%对PBS的62.5%)。因此,CF17在体外以剂量和时间依赖的方式有效地感染、复制和杀死GC细胞。在体内,腹腔注射CF17治疗对侵袭性GCPM模型表现出强大的抗肿瘤活性,以减少肿瘤负担,提高生存率,并防止腹水形成。这些临床前结果为CF17用于GCPM患者腹膜直接治疗的未来临床试验的设计提供了依据。
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Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases.

Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines in vitro and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner in vitro. In vivo, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.

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来源期刊
Molecular Therapy Oncolytics
Molecular Therapy Oncolytics Medicine-Oncology
CiteScore
10.90
自引率
3.50%
发文量
152
审稿时长
6 weeks
期刊介绍: Molecular Therapy — Oncolytics is an international, online-only, open access journal focusing on the development and clinical testing of viral, cellular, and other biological therapies targeting cancer.
期刊最新文献
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