华南理工大学熊梦华小组近日取得一项新成果。经过不懈努力，他们研究出膜溶肽计划免疫原性细胞死亡癌症治疗。相关论文于2026年8月5日发表于国际顶尖学术期刊《自然》杂志上。

在这里，研究组在肿瘤细胞中设计并实现了一种独特的免疫原性膜溶解细胞死亡（mLCD）模式，其特征是从溶酶体到质膜的时间滞后破裂；这种方法被发现可以有效地增强免疫检查点阻断治疗。这种模式的mLCD是由合成酸反应性膜解肽（aMP） aMPC16-CA50诱导的，它对与肿瘤细胞外环境和溶酶体相关的pH降低表现出分层响应。aMPC16-CA50激活了肿瘤细胞中的炎症转录程序，增强了它们诱导树突状细胞I类主要组织相容性复合体分子上抗原呈递的能力，并随后激活T细胞。溶膜肽的pH响应动力学和溶膜活性通过对膜破裂过程的时空调节，在增强溶瘤细胞的免疫原性方面起着关键作用。

此外，aMPC16-CA50通过促进抗肿瘤免疫应答，在增强免疫检查点阻断治疗的抗肿瘤疗效方面表现出相当大的优势。

此外，其全身给药在小鼠中耐受性良好。总的来说，研究人员通过对膜破裂过程的时空调节，成功地在肿瘤细胞中编程了一种独特的免疫原性mLCD模式，并合成了一种易于操作的pH反应性膜解肽。

据介绍，促进创新细胞死亡模式的合理设计可以极大地促进抗肿瘤治疗的进展。

附：英文原文

Title: Membranolytic peptide programs immunogenic cell death for cancer therapy

Author: Yuan, Yueling, Liang, Lifang, Li, Jie, Li, Chengrun, Wang, Fuxiang, Yan, Kai, Su, Chanjuan, Chen, Jingxian, Lan, Fan, Wu, Zining, Du, Rupei, Zhou, Yaofeng, Xiang, Xiongwei, Xu, Jueqiong, Zhou, Huosheng, Zou, Long, Zhang, Zhouming, Zhang, Yuhao, Huang, Songyin, Zhang, Yajing, Zhou, Penghui, Sun, Tianmeng, Yang, Kaiting, Zhao, Zhibin, Lian, Zhexiong, Xiao, Shiyan, Cheng, Jianjun, Bao, Yan, Xiong, Menghua

Issue&Volume: 2026-08-05

Abstract: A rational design for facilitating innovative cell death modes can substantially aid advances in antitumour therapy1,2. Here we design and implement a unique mode of immunogenic membranolytic cell death (mLCD) in tumour cells, characterized by time-lagged rupture from the lysosomal to plasma membranes; this approach was found to robustly potentiate immune checkpoint blockade therapy. This mode of mLCD was induced by the synthetic-acid-responsive membranolytic peptide (aMP) aMPC16-CA50, which exhibits hierarchical responsiveness to the decreasing pH associated with the tumour extracellular environment and lysosomes. aMPC16-CA50 activated an inflammatory transcriptional program in tumour cells, potentiating their ability to induce antigen presentation on class I major histocompatibility complex molecules on dendritic cells and the subsequent activation of T cells. The pH-responsive kinetics and membranolytic activity of the membranolytic peptides had a critical role in enhancing the immunogenicity of lytic tumour cells through the spatiotemporal regulation of the membrane-rupture processes. Furthermore, aMPC16-CA50 exhibited a considerable advantage in enhancing the antitumour efficacy of immune checkpoint blockade therapy through the promotion of antitumour immune response. Moreover, its systemic administration was well tolerated in mice. Overall, we successfully programmed a unique mode of immunogenic mLCD in tumour cells through the spatiotemporal regulation of membrane-rupture processes using a synthetic pH-responsive membranolytic peptide amenable to manipulation.

DOI: 10.1038/s41586-026-10899-5

Source: https://www.nature.com/articles/s41586-026-10899-5