Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T‐Cells |
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| Authors: | Fatemeh S. Majedi Mohammad Mahdi Hasani‐Sadrabadi Yoko Kidani Timothy J. Thauland Alireza Moshaverinia Manish J. Butte Steven J. Bensinger Louis‐S. Bouchard |
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| Affiliation: | 1. Department of Bioengineering, University of California, Los Angeles, CA, USA;2. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA;3. Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA, USA;4. Parker H. Petit Institute for Bioengineering and Bioscience, G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA;5. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA;6. Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California, Los Angeles, CA, USA;7. Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA, USA;8. The Molecular Biology Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA;9. California NanoSystems Institute, University of California, Los Angeles, CA, USA |
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| Abstract: | T‐cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T‐cells into the tumor environment. To facilitate T‐cell activation and differentiation in vitro, core–shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin‐2 (IL‐2), the major T‐cell growth factor, over 10+ d. The controlled delivery of cytokines is used to steer lineage specification of cultured T‐cells. This approach enables differentiation of T‐cells into central memory and effector memory subsets. It is shown that the sustained release of stromal cell‐derived factor 1α could accelerate T‐cell migration. It is demonstrated that CD4+ T‐cells could be induced to high concentrations of regulatory T‐cells through controlled release of IL‐2 and transforming growth factor beta. It is found that CD8+ T‐cells that received IL‐2 from microparticles are more likely to gain effector functions as compared with traditional administration of IL‐2. Culture of T‐cells within 3D scaffolds that contain IL‐2‐secreting microparticles enhances proliferation as compared with traditional, 2D approaches. This yield a new method to control the fate of T‐cells and ultimately to new strategies for immune therapy. |
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| Keywords: | cytokine delivery microfluidics microparticles T‐cells |
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