Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy

Shae, Daniel; Becker, Kyle W.; Christov, Plamen P.; Yun, Dong Soo; Lytton-Jean, Abigail K. R.; Sevimli, Sema; Ascano, Manuel; Kelley, Mark C.; Johnson, Douglas B.; Balko, Justin M.; Wilson, John T.

doi:10.1038/s41565-018-0342-5

Cited by 501 publications

(495 citation statements)

References 57 publications

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“…To avoid the degradation and ensure maximal phagocyte internalization of CDNs, endosomolytic nanoparticles have been designed to package and deliver CDNs. For example, pH-sensitive nanoparticles (e.g., STINGnanoparticles) can release their contents if located in acidic endosomal environments (269).…”

Section: Targeting the Cgas-sting Pathway For Treatmentmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

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Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immunesurveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states.

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Section: Targeting the Cgas-sting Pathway For Treatmentmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

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“…The nanocarrier contained a poly(beta‐amino ester) hydrogel mixed with DNA in its core, surrounded by a shell of PGS conjugated to T cell targeting ligands. Most recently, Wilson and co‐workers developed endosomolytic polymersomes to increase the activity of cGAMP (a STING agonist) to inhibit tumor growth, promote survival, and increase immune memory …”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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“…In contrast, targeted delivery of antigenic material directly into the cytosol can allow CD8 + T cell stimulation while bypassing endogenous cross‐presentation mechanisms. For cancer vaccine applications, effective cytosolic delivery can benefit both antigen and adjuvant, leading to simultaneous enhancement of antigen presentation and improvement of immune stimulation . In one example, a synthetic polymeric nanoparticle was used to deliver OVA to the cytosol while simultaneously triggering the stimulator of interferon gene (STING) pathway .…”

Section: Current Vaccine Nanotechnologymentioning

confidence: 99%

Biomimetic Nanotechnology toward Personalized Vaccines

et al. 2019

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While traditional approaches for disease management in the era of modern medicine have saved countless lives and enhanced patient well‐being, it is clear that there is significant room to improve upon the current status quo. For infectious diseases, the steady rise of antibiotic resistance has resulted in super pathogens that do not respond to most approved drugs. In the field of cancer treatment, the idea of a cure‐all silver bullet has long been abandoned. As a result of the challenges facing current treatment and prevention paradigms in the clinic, there is an increasing push for personalized therapeutics, where plans for medical care are established on a patient‐by‐patient basis. Along these lines, vaccines, both against bacteria and tumors, are a clinical modality that could benefit significantly from personalization. Effective vaccination strategies could help to address many challenging disease conditions, but current vaccines are limited by factors such as a lack of potency and antigenic breadth. Recently, researchers have turned toward the use of biomimetic nanotechnology as a means of addressing these hurdles. Recent progress in the development of biomimetic nanovaccines for antibacterial and anticancer applications is discussed, with an emphasis on their potential for personalized medicine.

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Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy

Cited by 501 publications

References 57 publications

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Materials for Immunotherapy

Biomimetic Nanotechnology toward Personalized Vaccines

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