Protein-only Nanoparticles for T Cell Expansion and Activation
Fornt Suñé, Marc (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Lázaro Bermejo, Gonzalo (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Gil Garcia, Marcos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Aran, Andrea (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Garcia-Pardo, Javier (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Martí, Mercè (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2024
Resum:	The in vitro expansion and activation of T cells utilizing synthetic nanosized artificial antigen presenting cells (aAPCs) have emerged as a promising technique for cancer treatment. Although diverse nanomaterials have been explored as aAPC scaffolds, protein-only nanoparticles have been largely overlooked, despite their high designability and biocompatibility. In this study, we exploit a plug-and-play approach for the development of protein-only nanoparticles as aAPCs using the self-assembling properties of ZapB coiled coil and the Z-domain antibody-capturing ability. The resulting coiled coil-based nanoparticles (ccNPs) can be easily, rapidly, and simultaneously functionalized with anti-CD3 and anti-CD28 antibodies (ccNPs-CD3/CD28). Our results demonstrate that ccNPs-CD3/CD28 induce polyclonal T cell proliferation and activation while sustaining cytokine production for an extended period. The biocompatibility, modularity, and chemistry-free surface modification of this protein-only strategy render it a versatile platform for in vitro T cell expansion and activation.
Ajuts:	Agencia Estatal de Investigación PID2019-105017RB-I00 Ministerio de Educación, Cultura y Deporte FPU16/02465 Ministerio de Ciencia e Innovación IJC2019-041039-I
Nota:	Altres ajuts: acords transformatius de la UAB
Nota:	This work was funded by the Spanish Ministry of Science and Innovation (PID2019-105017RB-I00), by ICREA, ICREA-Academia 2020, to S.V., and by Fundación Contigo Contra el Cáncer de la Mujer (#BREASTILs. Functional Study of TILs from breast cancer patients: an approach to personalized medicine) to M.M. M.F.-S. was supported by the Spanish Ministry of Science and Innovation (FPU20/02897). G.L.B. was supported by the Universitat Autònoma de Barcelona (PIF 2021-22 B21P0025). M.G.-G. was supported by the Spanish Ministry of Science and Innovation (FPU16/02465). A.A. was supported by Fundación Contigo Contra el Cáncer de la Mujer. J.G-P. was supported by the Spanish Ministry of Science and Innovation with a Juan de la Cierva Incorporación IJC2019-041039-I. The authors thank the members of the Microscopy Service of the Universitat Autònoma de Barcelona for their technical support in electron microscopy and confocal imaging. We also thank the Cell Culture, Antibody Production and Cytometry Service and, specially, Manuela Costa for the technical support in Flow Cytometry analyses. We thank Andrea Livieri for her help in endotoxin measurements.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Protein nanoparticles ; Self-assembly ; Coiled coil ; Z-domain ; Antibody ; T cell activation ; T cell proliferation
Publicat a:	ACS applied nano materials, Vol. 7 Núm. 6 (22 2024) , p. 6669-6680, ISSN 2574-0970

DOI: 10.1021/acsanm.4c00698

12 p, 5.7 MB

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