pH and ROS Responsiveness of Polymersome Nanovaccines for Antigen and Adjuvant Codelivery: An In Vitro and In Vivo Comparison

Jäger, Eliézer; Ilina, Olga; Dölen, Yusuf; Valente, Michael; van Dinther, Eric A.W.; Jäger, Alessandro; Figdor, Carl G.; Verdoes, Martijn

doi:10.1021/acs.biomac.3c01235

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…Moreover, in vitro T cell suppression assays showed that rapamycin-loaded NPs exhibited similar or even better inhibitory performance to CD4 + and CD8 + cells than free rapamycin at different rapamycin concentrations (Figure c). This NP matrix degradation-determined release raises our possibility to precisely control the therapeutic window of drugs, and this stability against environmental influences can reduce premature release and enhance the in vivo performance of NPs . In another case, Little et al demonstrated that a MP system, which slowly releases a T reg -recruiting chemokine in a linear fashion, prevented rejection and promoted hindlimb allograft survival (>200 days) in a rat model …”

Section: Design Of Functional Particles For T Cell-based Immunomodula...mentioning

confidence: 99%

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: Design Of Functional Particles For T Cell-based Immunomodula...mentioning

confidence: 99%