Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model.

Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model.
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DOI:
10.1080/2162402x.2017.1338236
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发表时间:
2017
期刊:
影响因子:
7.2
通讯作者:
Rekdal Ø
Rekdal Ø
中科院分区:
医学2区
文献类型:
--
作者:
Nestvold J;Wang MY;Camilio KA;Zinöcker S;Tjelle TE;Lindberg A;Haug BE;Kvalheim G;Sveinbjørnsson B;Rekdal Ø

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LTX 315是一种具有强效免疫学特性的溶瘤肽。在本研究中,我们证明了用LTX-315进行瘤内治疗导致大鼠纤维肉瘤模型中的完全消退和全身免疫应答。治疗具有T细胞依赖性,并且还导致远端效应,如远端未治疗病变消退所示。免疫组化和流式细胞术分析显示,在治疗和未治疗的病变中均观察到显著的CD 8 + T细胞浸润。LTX-315在体外以裂解作用模式快速杀死细胞,随后释放危险相关分子模式(DAMP)分子,如HMGB 1、ATP和细胞色素c。总之,我们的数据表明,LTX-315代表了一种新的癌症免疫治疗方法,具有作为新型免疫抑制剂的潜力。
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8+ T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis. LTX-315 rapidly killed the cells in vitro with a lytic mode of action followed by the subsequent release of Danger-Associated Molecular Pattern (DAMP) molecules such as HMGB1, ATP and Cytochrome c. Together, our data demonstrate that LTX-315 represents a new approach to cancer immunotherapy, which has the potential as a novel immunotherapeutic agent.