Degradation-regulated architecture of injectable smart hydrogels enhances humoral immune response and potentiates antitumor activity in human lung carcinoma

Duong, Huu Thuy Trang; Thambi, Thavasyappan; Yin, Yue; Kim, Seong Han; Nguyen, Thanh Loc; Phan, Vu To-Anh; Kim, Jaeyun; Jeong, Ji Hoon; Lee, Sang Soo

doi:10.1016/j.biomaterials.2019.119599

Cited by 80 publications

(50 citation statements)

References 55 publications

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“…Targeting multiple epitopes allows for a wider spectrum of antigens that expanded T cells can recognize within heterogenous tumor cell populations. Further, potent anti-tumor responses arise from simultaneous induction of both humoral and cellular responses, requiring different epitopes to activate B cells and multiple subsets of T-cells (42)(43)(44). Thus, there is also motivation to test if multiple epitopes can be incorporated into polyplexes.…”

Section: Discussionmentioning

confidence: 99%

Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination

2021

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Biomaterial delivery systems offer unique potential to improve cancer vaccines by offering targeted delivery and modularity to address disease heterogeneity. Here, we develop a simple platform using a conserved human melanoma peptide antigen (Trp2) modified with cationic arginine residues that condenses an anionic toll-like receptor agonist (TLRa), CpG, into polyplex-like nanoparticles. We reasoned that these structures could offer several useful features for immunotherapy – such as tunable loading, co-delivery of immune cues, and cargo protection – while eliminating the need for synthetic polymers or other complicating delivery systems. We demonstrate that Trp2/CpG polyplexes can readily form over a range of Trp2:CpG ratios and improve antigen uptake by primary antigen presenting cells. We show antigen loading can be tuned by interchanging Trp2 peptides with defined charges and numbers of arginine residues. Notably, these polyplexes with greater antigen loading enhance the functionality of Trp-2 specific T cells and in a mouse melanoma model, decrease tumor burden and improve survival. This work highlights opportunities to control the biophysical properties of nanostructured materials built from immune signals to enhance immunotherapy, without the added complexity or background immune effects often associated with synthetic carriers.

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Section: Discussionmentioning

confidence: 99%

Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination

2021

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“…Despite the fact that the substantial improvement achieved by conventional cancer vaccines, the risk of undetected contaminations during the elaborate preparation process and the high costs associated with preparation and storage remain bottlenecks limiting their broad clinical implementation ( Duong et al, 2020a ). In situ vaccination (ISV), without the need for previous identification and isolation of tumor antigens, is raising great attention in cancer immunotherapy.…”

Section: In Situ Cancer Vaccinesmentioning

confidence: 99%

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines

et al. 2021

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Cancer vaccines represent among the most promising strategies in the battle against cancers. However, the clinical efficacy of current cancer vaccines is largely limited by the lack of optimized delivery systems to generate strong and persistent antitumor immune responses. Moreover, most cancer vaccines require multiple injections to boost the immune responses, leading to poor patient compliance. Controlled-release drug delivery systems are able to address these issues by presenting drugs in a controlled spatiotemporal manner, which allows co-delivery of multiple drugs, reduction of dosing frequency and avoidance of significant systemic toxicities. In this review, we outline the recent progress in cancer vaccines including subunit vaccines, genetic vaccines, dendritic cell-based vaccines, tumor cell-based vaccines and in situ vaccines. Furthermore, we highlight the efforts and challenges of controlled or sustained release drug delivery systems (e.g., microparticles, scaffolds, injectable gels, and microneedles) in ameliorating the safety, effectiveness and operability of cancer vaccines. Finally, we briefly discuss the correlations of vaccine release kinetics and the immune responses to enlighten the rational design of the next-generation platforms for cancer therapy.

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“…[108,109] Moreover, metal-based NPs,s uch as gold [110] and iron oxide NPs, [111,112] liposomes, [113][114][115] and ar ange of hydrogels have been used in combination with biopolymers to introduce new functionalities. [99,116,117] When designing DNAvaccine carrier materials,different biological barriers need to be taken into account. On an extracellular level, these include the rapid clearance of foreign genetic material from the bloodstream, deactivation through serum proteins,a nd degradation of DNAt hrough DNases.Once the target cell is reached, carrier-bound DNA needs to be internalised through the membrane via phago-, pino-, or endocytosis.F inally,u pon internalisation, the vaccine is required to escape phago-or endosomal vesicles and travel across the cytoplasm to reach the nucleus,w here DNAn eeds to dissociate from the carrier to enable the expression of the encoded antigen.…”

Section: Design Of Biopolymer Vaccine Carriersmentioning

confidence: 99%

Biopolymer‐based Carriers for DNA Vaccine Design

et al. 2021

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She studied chemistry at the University of Zagreb, and completed her PhD at the University of Strathclyde,G lasgow,w orking on DNA detection by advanced spectroscopies, such as SERRS. After postdoc research on DNA nanostructuring and artificial enzyme design at the University of Dortmund,s he was agroup leader at Karlsruhe Institute of Technology before joining Cambridge. Her research focuses on nanostructured biomaterials for use in photocatalysis and targeted drug delivery.

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Degradation-regulated architecture of injectable smart hydrogels enhances humoral immune response and potentiates antitumor activity in human lung carcinoma

Cited by 80 publications

References 55 publications

Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination

Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines

Biopolymer‐based Carriers for DNA Vaccine Design

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