Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membrane-decorated nanoparticles

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外文摘要：Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocom-patibility complex Ⅰ(MHC-Ⅰ)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-Ⅰ-deficient TNBC.SIRPα on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells.The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds.LMNs also block CD47-mediated phagocytosis suppression.LMNs inhibit the growth of MHC-Ⅰ-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important roles.This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-Ⅰ-deficient cancers.

外文关键词：

MHC-Ⅰ deficiencyMacrophageCD47ImmunotherapyTriple-negative breast cancerPhagocytosisImmune checkpointInnate immunity

作者：

Wen Zhang、Yihui Zhai、Ying Cai、Xiang Gong、Yunxuan Jiang、Rong Rong、Chao Zheng、Binyu Zhu、Helen He Zhu、Hao Wang、Yaping Li、Pengcheng Zhang

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作者单位：

China State Institute of Pharmaceutical Industry,Shanghai 201203,China

State Key Laboratory of Drug Research & Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

University of Chinese Academy of Sciences,Beijing 100049,China

School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China

Yantai Institute of Materia Medica,Shandong 264000,China

State Key Laboratory of Oncogenes and Related Genes,Renji-Med-X Stem Cell Research Center,Department of Urology,Ren Ji Hospital,School of Medicine and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai 200127,China

School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices,ShanghaiTech University,Shanghai 201210,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShandong Laboratory Program,China

项目编号：

323714573217137432130058SYS202205

出版年：

2024

DOI：

10.1016/j.apsb.2024.04.009

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(7)