魏茨曼科学研究所Ido Amit团队在研究中取得进展。他们探明了巨噬细胞靶向免疫细胞因子利用骨髓、T和NK细胞协同作用进行癌症免疫治疗。相关论文于2025年11月19日发表于国际顶尖学术期刊《细胞》杂志上。
课题组人员开发了骨髓靶向免疫细胞因子和自然杀伤(NK)/T细胞增强剂（MiTEs），利用骨髓和淋巴细胞协同作用进行免疫治疗。MiTEs是具有肿瘤特异性激活的反式免疫细胞因子，可以通过TREM2拮抗和通过白细胞介素(IL)-2激活细胞毒性效应细胞双重靶向TAMs和淋巴细胞。为了避免脱靶毒性，MiTEs含有IL-2掩膜片段，该片段被TAM特异性蛋白酶切割。MiTEs在临床前肿瘤模型中通过跨越TAM、T和NK细胞区室的广泛免疫重编程显示出很高的疗效。MiTEs通过诱导强效多轴抗肿瘤免疫，同时将毒性降至最低，显示出治疗实体癌的变革性潜力。
据悉，表达髓系检查点TREM2的肿瘤相关巨噬细胞（tumor associated macrophages, TAMs）是肿瘤微环境（tumor microenvironment， TME）中关键的免疫抑制细胞，驱动肿瘤进展，导致癌症患者预后不良。由于它们的关键作用，TAMs已成为免疫治疗的一个有希望的靶点。然而，目前针对TAM的单一疗法显示出有限的疗效，这突出表明需要采用多种免疫模式的策略。
附：英文原文
Title: Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy
Author: Michelle von Locquenghien, Pascale Zwicky, Ken Xie, Diego Adhemar Jaitin, Fadi Sheban, Adam Yalin, Florian Uhlitz, Chamutal Gur, Reut Sharet Eshed, Eyal David, Kfir Mazuz, Caroline Jennings Marin, Ankita Sankar, Devin Mediratta, Roberto Avellino, Assaf Weiner, Ido Amit
Issue&Volume: 2025-11-19
Abstract: Tumor-associated macrophages (TAMs) expressing the myeloid checkpoint TREM2 are key immunosuppressive cells in the tumor microenvironment (TME), driving tumor progression and contributing to poor prognosis in cancer patients. Due to their pivotal role, TAMs have emerged as a promising target for immunotherapies. However, current TAM-targeting monotherapies show limited efficacy, highlighting the need for strategies engaging multiple immune modalities. Here, we developed myeloid-targeted immunocytokines and natural killer (NK)/T cell enhancers (MiTEs) harnessing myeloid and lymphoid synergy for immunotherapy. MiTEs are trans-acting immunocytokines with tumor-specific activation, allowing dual targeting of TAMs and lymphocytes by TREM2 antagonism and cytotoxic effector cell activation through interleukin (IL)-2. To avoid off-target toxicities, MiTEs contain an IL-2 masking moiety, which is cleaved by a TAM-specific protease. MiTEs demonstrate high efficacy in preclinical tumor models through extensive immune reprogramming spanning TAM, T, and NK cell compartments. MiTEs show transformative potential for treating solid cancers by inducing potent multi-axis anti-tumor immunity while minimizing toxicities.
DOI: 10.1016/j.cell.2025.10.030
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01235-8