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LTX-315:一种一流的溶瘤肽,可重编程肿瘤微环境。

LTX-315: a first-in-class oncolytic peptide that reprograms the tumor microenvironment.

作者信息

Sveinbjørnsson Baldur, Camilio Ketil Andre, Haug Bengt Erik, Rekdal Øystein

机构信息

Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, NO-9037 Tromsø, Norway.

Lytix Biopharma, Gaustadalléen 21, NO-0349 Oslo, Norway.

出版信息

Future Med Chem. 2017 Aug;9(12):1339-1344. doi: 10.4155/fmc-2017-0088. Epub 2017 May 11.

Abstract

The oncolytic peptide LTX-315, which has been de novo designed based on structure-activity relationship studies of host defense peptides, has the ability to kill human cancer cells and induce specific anticancer immune response when injected locally into tumors established in immunocompetent mice. The oncolytic effect of LTX-315 involves perturbation of plasma membrane and the mitochondria with subsequent release of danger-associated molecular pattern molecules, which highlights the ability of LTX-315 to induce complete regression and protective immune responses. Treatment with LTX-315 reprograms the tumor microenvironment by decreasing the local abundance of immunosuppressive cells and by increasing the frequency of effector T cells.

摘要

溶瘤肽LTX-315是基于宿主防御肽的构效关系研究而全新设计的,当将其局部注射到免疫健全小鼠体内建立的肿瘤中时,它具有杀死人类癌细胞并诱导特异性抗癌免疫反应的能力。LTX-315的溶瘤作用涉及质膜和线粒体的扰动,随后释放危险相关分子模式分子,这突出了LTX-315诱导完全消退和保护性免疫反应的能力。用LTX-315治疗可通过降低免疫抑制细胞的局部丰度和增加效应T细胞的频率来重新编程肿瘤微环境。

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