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Integrated microfluidics-based construction of anti-BTN2A2 gel droplet cell preparations for non-invasive tumor-infiltrating lymphocyte therapy.

作者信息

Tian Yishen, Li Jingxuan, Yang Na, Zhao Yang, Zuo Jiancao, Xiong Hang, Pan Yiwen, Xiao Li, Su Min, Han Feng, He Zhixu, Hu Rong

机构信息

Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, 550025, China.

Key Laboratory for Research on Autoimmune Diseases of Higher Education Schools in Guizhou Province, Guiyang, 550025, China.

出版信息

Mater Today Bio. 2025 Feb 4;31:101545. doi: 10.1016/j.mtbio.2025.101545. eCollection 2025 Apr.


DOI:10.1016/j.mtbio.2025.101545
PMID:40026625
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11869011/
Abstract

Tumor infiltrating lymphocyte therapy (TIL therapy) is one of the effective treatments for solid tumors. However, certain periods or sites of solid tumors are not amenable to surgical resection. Meanwhile, the abundant and dense extracellular matrix (ECM) and regulatory cells (e.g., regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC)) in solid tumors when infused back into the treatment will prevent T cell infiltration and proliferation, thus inhibiting the efficacy of this approach. In this study, a novel cell preparation was successfully developed by integrating microfluidic chip design with carbodiimide chemical modification. This preparation was surface modified with BTN2A2 antibodies and internally contained T cells isolated from the blood of tumor hosts, along with simulated collagen peptide CMP. Specifically, the cell preparation exerted its anti-tumor effects through multiple mechanisms: Firstly, the surface BTN2A2 antibodies effectively inhibited the proliferation of Tregs and MDSCs within the tumor microenvironment; Secondly, leveraging the T cell antigen receptors (TCRs) present in the blood T cells, which were similar to those of tumor-infiltrating lymphocytes, significantly enhanced their targeting and cytotoxic capabilities; Furthermore, the CMP component within the droplets effectively promoted the infiltration of T cells into tumor tissues. In the complex immunosuppressive microenvironment, the synergistic action of these components markedly enhanced the clearance efficacy of the immune system. Experimental results demonstrated that this cellular preparation exhibited promising therapeutic effects in both melanoma and pancreatic cancer models. This research provided a novel platform for the synergistic cooperation of various methods in tumor immunotherapy, holding broad application prospects.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/f3697e4aebba/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/65f936d49b92/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/f14ca537219f/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/5aa5eeb3811b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/93f8ce85dd5c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/d468d91d3dfe/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/6a87d3433c71/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/f3697e4aebba/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/65f936d49b92/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/f14ca537219f/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/5aa5eeb3811b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/93f8ce85dd5c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/d468d91d3dfe/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/6a87d3433c71/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f115/11869011/f3697e4aebba/gr5.jpg

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[1]
Integrated microfluidics-based construction of anti-BTN2A2 gel droplet cell preparations for non-invasive tumor-infiltrating lymphocyte therapy.

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[2]
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引用本文的文献

[1]
An antibody targeting an immune checkpoint molecule BTN2A2 enhances anti-tumor immunity.

Neoplasia. 2025-7

本文引用的文献

[1]
CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia.

J Transl Med. 2024-3-13

[2]
Microfluidic-based preparation of artificial antigen-presenting gel droplets for integrated and minimalistic adoptive cell therapy strategies.

Biofabrication. 2024-3-15

[3]
Clinical immunotherapy in pancreatic cancer.

Cancer Immunol Immunother. 2024-3-2

[4]
Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy.

J Immunother Cancer. 2024-2-29

[5]
FDA approves first tumour-infiltrating lymphocyte (TIL) therapy, bolstering hopes for cell therapies in solid cancers.

Nat Rev Drug Discov. 2024-4

[6]
Expanding CAR-T cell immunotherapy horizons through microfluidics.

Lab Chip. 2024-2-27

[7]
BTN2A2, a new biomarker and therapeutic target for glioma.

Aging (Albany NY). 2023-10-17

[8]
Development of a microfluidic cell transfection device into gene-edited CAR T cell manufacturing workflow.

Lab Chip. 2023-11-7

[9]
Challenges and new technologies in adoptive cell therapy.

J Hematol Oncol. 2023-8-18

[10]
Microfluidic Chips: Emerging Technologies for Adoptive Cell Immunotherapy.

Micromachines (Basel). 2023-4-19

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