| 1. |
- Moran, Hannah B T, et al.
(author)
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Immunomodulatory properties of chitosan polymers
- 2018
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In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 184, s. 1-9
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Journal article (peer-reviewed)abstract
- The introduction of vaccines is regarded as one of the most successful medical interventions to date. However, there is a clear need for the development of new vaccines for diseases which require the induction of a potent cellular immune response. Advancements in the field of vaccine research have resulted in a move away from the use of whole organisms and towards the use of subunit vaccines which consist of highly purified antigens with an improved safety profile. Adjuvants are immunostimulatory components that are included in subunit vaccine formulations to help direct and amplify adaptive immune responses. Chitosan is a cationic polysaccharide that has been examined in an adjuvant setting due to its biocompatible and biodegradable nature. The polysaccharide has been shown to have the capacity to induce Th1 cell responses following vaccination by injection or mucosal routes, supporting its application as an alternative to alum for vaccines that promote cell-mediated immunity. Here, we provide an overview of the physico-chemical properties of chitosan with a focus on the specific characteristics that dictate the type and scale of the immune responses induced. The potential to finely tailor chitosan polymers in order to direct specific types of immune responses can provide invaluable tools for the design of novel chitosan-based adjuvants and biomaterials.
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| 2. |
- Turley, Joanna L., et al.
(author)
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Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8+ T cell-dependent anti-tumor immunity
- 2024
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In: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 5:5
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Journal article (peer-reviewed)abstract
- Stimulator of IFN genes (STING) is a promising target for adjuvants utilized in in situ cancer vaccination approaches. However, key barriers remain for clinical translation, including low cellular uptake and accessibility, STING variability necessitating personalized STING agonists, and interferon (IFN)-independent signals that can promote tumor growth. Here, we identify C100, a highly deacetylated chitin-derived polymer (HDCP), as an attractive alternative to conventional STING agonists. C100 promotes potent anti-tumor immune responses, outperforming less deacetylated HDCPs, with therapeutic efficacy dependent on STING and IFN alpha/beta receptor (IFNAR) signaling and CD8+ T cell mediators. Additionally, C100 injection synergizes with systemic checkpoint blockade targeting PD-1. Mechanistically, C100 triggers mitochondrial stress and DNA damage to exclusively activate the IFN arm of the cGAS-STING signaling pathway and elicit sustained IFNAR signaling. Altogether, these results reveal an effective STING- and IFNAR-dependent adjuvant for in situ cancer vaccines with a defined mechanism and distinct properties that overcome common limitations of existing STING therapeutics.
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