Semi‐Flexible Immunobrushes Facilitate Effective and Selective Expansion of Antigen‐Specific T Cells

Gerrits, Lotte; Weiss, Lea; Grad, Emilia M.; Schluck, Marjolein; Maassen, Lisa; Classens, René; Archidi, Chadia; Verdoes, Martijn; Figdor, Carl G.; Kouwer, Paul H. J.; Hammink, Roel

doi:10.1002/adfm.202307606

Cited by 1 publication

(2 citation statements)

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“…Figdor and co-workers coated SIINFEKLbound MHC and anti-CD28-conjugated semiflexible poly-(isocyanopeptide) immunofilaments on magnetic beads to mimic a fluidic membrane, strongly amplifying and enriching antigen-specific T cells by more than 90-fold in 7 days. 22 DNA scaffolds have recently emerged as a new class of materials for T cell regulation. Precise spatial control of ligand presentation on aAPCs can be exploited to engineer ligand− receptor interactions and allow for quantitative analysis at single-particle resolution.…”

Section: Methodsmentioning

confidence: 99%

“…In a murine melanoma model, injection of the expanded lymphocytes directly into tumors was shown to significantly delay tumor growth. Figdor and co-workers coated SIINFEKL-bound MHC and anti-CD28-conjugated semiflexible poly(isocyanopeptide) immunofilaments on magnetic beads to mimic a fluidic membrane, strongly amplifying and enriching antigen-specific T cells by more than 90-fold in 7 days …”

Section: Methodsmentioning

confidence: 99%

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Engineering Functional Particles to Modulate T Cell Responses

Li,

Scheerstra

et al. 2024

Acc. Mater. Res.

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Metrics & MoreArticle Recommendations * sı Supporting Information CONSPECTUS: T cells play a critical role in adaptive immune responses. They work with other immune cells such as B cells to protect our bodies when the first line of defense, the innate immune system, is overcome by certain infectious diseases or cancers.Studying and regulating the responses of T cells, such as activation, proliferation, and differentiation, helps us understand not only their behavior in vivo but also their translation and application in the field of immunotherapy, such as adoptive T cell therapy and immune checkpoint therapy, the situations in which T cells cannot fight cancer alone and require external engineering regulation to help them. Nano-to micrometer-sized particulate biomaterials have achieved great progress in the assistance of T cell-based immunomodulation. For example, various types of microparticles decorated with T cell recognition and activation signals to mimic native antigen-presenting cells have shown successful ex vivo expansion of primary T cells and have been approved for clinical use in adoptive T cell therapy. Functional particles can also serve as vehicles for transporting cargos including small molecule drugs, cytokines, and antibodies. Especially for cargos with limited bioavailability and high repeat-dose toxicity, systemic administration in their free form is difficult. By using particle-assisted systems, the delivery can be tailored on demand, of which targeting and controlled release are two typical examples, ultimately aiding in the regulation of T cell responses. Furthermore, when T cells become overactive and behave in ways that contradict our expectations, such as attacking our own cells or innocuous foreign molecules, this can lead to a breakdown of immune tolerance. In such cases, particles to help reprogram those overactive T cells or suppress their activity are appreciated in vivo. The urgent need to introduce immune stimulation into the treatment of cancers, infectious diseases, and autoimmune diseases has driven recent advances in the engineering of functional particulate biomaterials that regulate T cell responses. In this Account, we will first cover a brief overview of the process of T cell-based immunomodulation from principle to development. It then outlines critical points in the design of functional particle platforms, including materials, size, morphology, surface engineering, and delivery of cargos, to modulate the features of T cells, and introduces selected work from our and other research groups with a focus on three major therapeutic applications: adoptive T cell therapy, immune checkpoint therapy, and immune tolerance restoration. Current challenges and future opportunities are also discussed.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%