牛痘病毒与肽受体放射治疗协同提高腹膜癌的治疗效果。

IF 5.3 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Kathryn Ottolino-Perry, David Mealiea, Clara Sellers, Sergio A Acuna, Fernando A Angarita, Lili Okamoto, Deborah Scollard, Mihaela Ginj, Raymond Reilly, J Andrea McCart
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引用次数: 0

摘要

肿瘤特异性受体的过表达使得多种靶向癌症治疗成为可能,例如针对生长抑素受体(SSTR)阳性神经内分泌肿瘤的肽受体放疗(PRRT)。PRRT虽然有效,但仅限于SSTR过表达的肿瘤。为了克服这一限制,我们建议使用溶瘤痘苗病毒(vvDD)介导的受体基因转移,在没有内源性SSTR过表达的肿瘤中进行分子成像和PRRT,这一策略被称为放射病毒治疗。我们假设vvDD-SSTR联合放射标记的生长抑素类似物可以作为放射病毒治疗在结直肠癌腹膜癌模型中使用,产生肿瘤特异性的放射肽积累。在vvDD-SSTR和177Lu-DOTATOC治疗后,对病毒复制和细胞毒性、生物分布、肿瘤摄取和生存进行了评估。放射病毒治疗没有改变病毒的复制或生物分布,但以受体依赖的方式协同改善了vvdd - sstr诱导的细胞杀伤,并显著增加了177Lu-DOTATOC的肿瘤特异性积累和肿瘤与血液的比率,使肿瘤可以通过显微spect /CT成像,且无明显毒性。177Lu-DOTATOC联合vvDD-SSTR而非对照病毒时,比单独使用病毒显著提高生存率。因此,我们证明了vvDD-SSTR可以将受体阴性肿瘤转化为受体阳性肿瘤,并促进分子成像和使用放射性标记的生长抑素类似物进行PRRT。放射病毒疗法是一种很有前途的治疗策略,在多种癌症中具有潜在的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.

Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and 177Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of 177Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. 177Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.

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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.
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