Genetically engineered membrane-based nanoengagers for immunotherapy of pancreatic cancer

© 2024. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

Journal of nanobiotechnology - 22(2024), 1 vom: 11. März, Seite 104

Sprache:

Englisch

Beteiligte Personen:

Zhang, Haoqi [VerfasserIn]
Li, Yuanke [VerfasserIn]
Kang, Helong [VerfasserIn]
Lan, Jingping [VerfasserIn]
Hou, Lin [VerfasserIn]
Chen, Zhengbang [VerfasserIn]
Li, Fan [VerfasserIn]
Liu, Yanqin [VerfasserIn]
Zhao, Jiliang [VerfasserIn]
Li, Na [VerfasserIn]
Wan, Yajuan [VerfasserIn]
Zhu, Yiping [VerfasserIn]
Zhao, Zhen [VerfasserIn]
Zhang, Hongkai [VerfasserIn]
Zhuang, Jie [VerfasserIn]
Huang, Xinglu [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Bispecific
CLDN18 protein, human
Cell membrane
Claudins
Journal Article
Macrophages
Nanoengagers
Pancreatic cancer

Anmerkungen:

Date Completed 13.03.2024

Date Revised 15.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s12951-024-02369-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369580168