Cell and biomaterial delivery strategies to induce immune tolerance

Scotland, Brianna L.; Shaw, Jacob R.; Dharmaraj, Shruti; Caprio, Nicholas; Cottingham, Andrea L.; Joy Martín Lasola, Jackline; Sung, Junsik J.; Pearson, Ryan M.

doi:10.1016/j.addr.2023.115141

Cited by 3 publications

(3 citation statements)

References 278 publications

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“…The selection and encapsulation modes of small molecule drugs, cytokines, and antibodies have been extensively summarized elsewhere. 49,50 Here, we would like to focus on the controlled release of these cargos and how these contribute to T cell modulation.…”

Section: Cargo Deliverymentioning

confidence: 99%

“…For ICT to reinvigorate the functions of T cells, anti-PD-1 and anti-CTLA-4 are popular options, and their encapsulation in NPs enhances their specificity and reduces off-target toxicity. The selection and encapsulation modes of small molecule drugs, cytokines, and antibodies have been extensively summarized elsewhere. , Here, we would like to focus on the controlled release of these cargos and how these contribute to T cell modulation.…”

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

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: Cargo Deliverymentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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“…To maintain the immune tolerant state, the body has employed both central and peripheral tolerance mechanisms. Central tolerance represents the known negative selection processes eliminating the self-reactive or autoreactive T cells in the thymus and bone marrow. , Peripheral tolerance inhibits activated T cells in peripheral tissues and secondary lymphoid organs. By employing multiple mechanisms, peripheral tolerance could impede the expansion of self-reactive/autoreactive T cells and restore immune homeostasis .…”

Section: Introductionmentioning

confidence: 99%

Tolerogenic Nano-/Microparticle Vaccines for Immunotherapy

Liu,

Chen,

Liu

et al. 2024

ACS Nano

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Autoimmune diseases, allergies, transplant rejections, generation of antidrug antibodies, and chronic inflammatory diseases have impacted a large group of people across the globe. Conventional treatments and therapies often use systemic or broad immunosuppression with serious efficacy and safety issues. Tolerogenic vaccines represent a concept that has been extended from their traditional immune-modulating function to induction of antigen-specific tolerance through the generation of regulatory T cells. Without impairing immune homeostasis, tolerogenic vaccines dampen inflammation and induce tolerogenic regulation. However, achieving the desired potency of tolerogenic vaccines as preventive and therapeutic modalities calls for precise manipulation of the immune microenvironment and control over the tolerogenic responses against the autoantigens, allergens, and/or alloantigens. Engineered nano-/microparticles possess desirable design features that can bolster targeted immune regulation and enhance the induction of antigen-specific tolerance. Thus, particle-based tolerogenic vaccines hold great promise in clinical translation for future treatment of aforementioned immune disorders. In this review, we highlight the main strategies to employ particles as exciting tolerogenic vaccines, with a focus on the particles' role in facilitating the induction of antigen-specific tolerance. We describe the particle design features that facilitate their usage and discuss the challenges and opportunities for designing nextgeneration particle-based tolerogenic vaccines with robust efficacy to promote antigen-specific tolerance for immunotherapy.

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