Genetically engineered membrane-based nanoengagers for immunotherapy of pancreatic cancer

被引：7

作者：

Zhang, Haoqi ^{[1
,2
]}

Li, Yuanke ^{[1
,2
]}

Kang, Helong ^{[1
,2
]}

Lan, Jingping ^{[1
,2
]}

Hou, Lin ^{[1
,2
]}

Chen, Zhengbang ^{[3
]}

Li, Fan ^{[1
,2
]}

Liu, Yanqin ^{[1
,2
]}

Zhao, Jiliang ^{[1
,2
]}

Li, Na ^{[1
,2
]}

Wan, Yajuan ^{[1
,2
]}

Zhu, Yiping ^{[1
,2
]}

Zhao, Zhen ^{[4
]}

Zhang, Hongkai ^{[1
,2
]}

Zhuang, Jie ^{[3
]}

Huang, Xinglu ^{[1
,2
]}

机构：

[1] Nankai Univ, Coll Life Sci, Minist Educ, State Key Lab Med Chem Biol,Key Lab Bioact Mat, Tianjin 300071, Peoples R China

[2] Nankai Univ, Frontiers Sci Ctr Cell Responses, Tianjin 300071, Peoples R China

[3] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

[4] Hebei Univ Technol, Inst Biophys, Sch Hlth Sci & Biomed Engn, Key Lab Mol Biophys Hebei Prov, Tianjin 300401, Peoples R China

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2024年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Nanoengagers; Macrophages; Cell membrane; Pancreatic cancer; IMMUNE SURVEILLANCE; MACROPHAGES; GEMCITABINE; STATISTICS; FOLFIRINOX; MECHANISMS; CARCINOMA; ANTIBODY;

D O I：

10.1186/s12951-024-02369-9

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive "cold" pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane.

引用

页数：14

共 45 条

[1] Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer [J].

Balachandran, Vinod P. ;

Luksza, Marta ;

Zhao, Julia N. ;

Makarov, Vladimir ;

Moral, John Alec ;

Remark, Romain ;

Herbst, Brian ;

Askan, Gokce ;

Bhanot, Umesh ;

Senbabaoglu, Yasin ;

Wells, Daniel K. ;

Cary, Charles Ian Ormsby ;

Grbovic-Huezo, Olivera ;

Attiyeh, Marc ;

Medina, Benjamin ;

Zhang, Jennifer ;

Loo, Jennifer ;

Saglimbeni, Joseph ;

Abu-Akeel, Mohsen ;

Zappasodi, Roberta ;

Riaz, Nadeem ;

Smoragiewicz, Martin ;

Kelley, Z. Larkin ;

Basturk, Olca ;

Goenen, Mithat ;

Levine, Arnold J. ;

Allen, Peter J. ;

Fearon, Douglas T. ;

Merad, Miriam ;

Gnjatic, Sacha ;

Iacobuzio-Donahue, Christine A. ;

Wolchok, Jedd D. ;

DeMatteo, Ronald P. ;

Chan, Timothy A. ;

Greenbaum, Benjamin D. ;

Merghoub, Taha ;

Leach, Steven D. .

NATURE, 2017, 551 (7681) :512-+

[2] Immune Cytolytic Activity Stratifies Molecular Subsets of Human Pancreatic Cancer [J].

Balli, David ;

Rech, Andrew J. ;

Stanger, Ben Z. ;

Vonderheide, Robert H. .

CLINICAL CANCER RESEARCH, 2017, 23 (12) :3129-3138

[3] CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans [J].

Beatty, Gregory L. ;

Chiorean, Elena G. ;

Fishman, Matthew P. ;

Saboury, Babak ;

Teitelbaum, Ursina R. ;

Sun, Weijing ;

Huhn, Richard D. ;

Song, Wenru ;

Li, Dongguang ;

Sharp, Leslie L. ;

Torigian, Drew A. ;

O'Dwyer, Peter J. ;

Vonderheide, Robert H. .

SCIENCE, 2011, 331 (6024) :1612-1616

[4] Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy [J].

Blanco, Belen ;

Dominguez-Alonso, Carmen ;

Alvarez-Vallina, Luis .

CLINICAL CANCER RESEARCH, 2021, 27 (20) :5457-5464

[5] Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].

Brahmer, Julie R. ;

Tykodi, Scott S. ;

Chow, Laura Q. M. ;

Hwu, Wen-Jen ;

Topalian, Suzanne L. ;

Hwu, Patrick ;

Drake, Charles G. ;

Camacho, Luis H. ;

Kauh, John ;

Odunsi, Kunle ;

Pitot, Henry C. ;

Hamid, Omid ;

Bhatia, Shailender ;

Martins, Renato ;

Eaton, Keith ;

Chen, Shuming ;

Salay, Theresa M. ;

Alaparthy, Suresh ;

Grosso, Joseph F. ;

Korman, Alan J. ;

Parker, Susan M. ;

Agrawal, Shruti ;

Goldberg, Stacie M. ;

Pardoll, Drew M. ;

Gupta, Ashok ;

Wigginton, Jon M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465

[6] The making of bispecific antibodies [J].

Brinkmann, Ulrich ;

Kontermann, Roland E. .

MABS, 2017, 9 (02) :182-212

[7]

Cho NH, 2011, NAT NANOTECHNOL, V6, P675, DOI [10.1038/NNANO.2011.149, 10.1038/nnano.2011.149]

[8] FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer [J].

Conroy, T. ;

Hammel, P. ;

Hebbar, M. ;

Ben Abdelghani, M. ;

Wei, A. C. ;

Raoul, J. -L. ;

Chone, L. ;

Francois, E. ;

Artru, P. ;

Biagi, J. J. ;

Lecomte, T. ;

Assenat, E. ;

Faroux, R. ;

Ychou, M. ;

Volet, J. ;

Sauvanet, A. ;

Breysacher, G. ;

Di Fiore, F. ;

Cripps, C. ;

Kavan, P. ;

Texereau, P. ;

Bouhier-Leporrier, K. ;

Khemissa-Akouz, F. ;

Legoux, J. -L. ;

Juzyna, B. ;

Gourgou, S. ;

O'Callaghan, C. J. ;

Jouffroy-Zeller, C. ;

Rat, P. ;

Malka, D. ;

Castan, F. ;

Bachet, J. -B. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (25) :2395-2406

[9] FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer [J].

Conroy, Thierry ;

Desseigne, Francoise ;

Ychou, Marc ;

Bouche, Olivier ;

Guimbaud, Rosine ;

Becouarn, Yves ;

Adenis, Antoine ;

Raoul, Jean-Luc ;

Gourgou-Bourgade, Sophie ;

de la Fouchardiere, Christelle ;

Bennouna, Jaafar ;

Bachet, Jean-Baptiste ;

Khemissa-Akouz, Faiza ;

Pere-Verge, Denis ;

Delbaldo, Catherine ;

Assenat, Eric ;

Chauffert, Bruno ;

Michel, Pierre ;

Montoto-Grillot, Christine ;

Ducreux, Michel .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (19) :1817-1825

[10] A Comprehensive High-Efficiency Protocol for Isolation, Culture, Polarization, and Glycolytic Characterization of Bone Marrow-Derived Macrophages [J].

Eshghjoo, Sahar ;

Kim, Da Mi ;

Jayaraman, Arul ;

Sun, Yuxiang ;

Alaniz, Robert C. .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2021, (168) :1-16

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