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携带溶瘤腺病毒的月经血干细胞克服了卵巢癌腹水对病毒活性的抑制作用。

Oncolytic Adenovirus-Loaded Menstrual Blood Stem Cells Overcome the Blockade of Viral Activity Exerted by Ovarian Cancer Ascites.

作者信息

Alfano Ana Laura, Nicola Candia Alejandro, Cuneo Nicasio, Guttlein Leandro N, Soderini Alejandro, Rotondaro Cecilia, Sganga Leonardo, Podhajcer Osvaldo L, Lopez M Veronica

机构信息

Laboratory of Molecular and Cellular Therapy, Fundación Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Buenos Aires C1405BWE, Argentina.

Servicio de Ginecología, Departamento de Cirugía, Hospital Municipal de Oncología Marie Curie, Avenida Patricias Argentinas 750, Buenos Aires C1405BWE, Argentina.

出版信息

Mol Ther Oncolytics. 2017 Jun 16;6:31-44. doi: 10.1016/j.omto.2017.06.002. eCollection 2017 Sep 15.

DOI:10.1016/j.omto.2017.06.002
PMID:28736743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5510493/
Abstract

Patients with ovarian cancer present peritoneal ascites at recurrence as a marker of disseminated disease and dismal prognosis. Oncolytic immunotherapy is an emerging approach for the treatment of disseminated cancer. In the present work, we constructed a novel oncolytic adenovirus, AR2011, to target malignant ovarian tumors. AR2011 exhibited a clear lytic effect in vitro in human ovarian cancer cell lines and malignant cells obtained from ascitic fluids (AFs) of patients with ovarian cancer. AR2011 activity was neutralized by antibodies present in 31 samples of patient-derived AFs. However, this blockade was overridden by preloading menstrual blood stem cells (MenSCs) with AR2011 (MenSC-AR), since AFs exerted no in vitro inhibitory effect on viral lytic activity under these conditions. Moreover, soluble factors present in AFs act as MenSC chemoattractants. MenSC-AR treatment of nude mice carrying established peritoneal carcinomatosis following administration of human ovarian cancer cells was able to inhibit tumor growth at levels similar to those observed with AR2011 alone. This study demonstrates that MenSCs can be used to override the blockade that AFs exert on viral oncolytic effects.

摘要

卵巢癌患者复发时会出现腹腔积液，这是疾病播散和预后不良的标志。溶瘤免疫疗法是一种新兴的治疗播散性癌症的方法。在本研究中，我们构建了一种新型溶瘤腺病毒AR2011，用于靶向恶性卵巢肿瘤。AR2011在体外对人卵巢癌细胞系以及从卵巢癌患者腹水中获得的恶性细胞具有明显的裂解作用。AR2011的活性被31份患者腹水样本中的抗体中和。然而，通过用AR2011预加载经血干细胞（MenSCs）（MenSC-AR）可以克服这种阻断作用，因为在这些条件下腹水对病毒裂解活性没有体外抑制作用。此外，腹水中存在的可溶性因子可作为MenSCs的趋化因子。在接种人卵巢癌细胞后对患有腹膜癌的裸鼠进行MenSC-AR治疗，能够抑制肿瘤生长，其抑制水平与单独使用AR2011时观察到的水平相似。这项研究表明，MenSCs可用于克服腹水对病毒溶瘤作用的阻断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/a68ed12d979b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/6eb15891ee2a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/23db0615615d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/f4fe4e524e71/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/4803bf9ba952/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/a68ed12d979b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/6eb15891ee2a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/23db0615615d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/f4fe4e524e71/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/4803bf9ba952/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6456/5510493/a68ed12d979b/gr5.jpg

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