Recent advances in carbohydrate-based cancer vaccines

Jin, Ketao; Lan, Huanrong; Chen, Xiaoyi; Wang, Shibing; Ying, Xiaojiang; Lin, Yan; Mou, Xiaozhou

doi:10.1007/s10529-019-02675-5

Cited by 32 publications

(32 citation statements)

References 45 publications

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“…We will discuss examples involving chemical modifications of the carbohydrates, especially the covalent conjugates of antigens and carbohydrate-based delivery carrier or adjuvants. Vaccines that contain carbohydrates and derivatives only as antigen components, or natural carbohydrates encapsulated/admixed with other vaccine components, have been reviewed (Marzabadi and Franck, 2017;Colombo et al, 2018;Wei et al, 2018;Weyant et al, 2018;Jin et al, 2019;Micoli et al, 2019), and are not discussed here.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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Vaccines are powerful tools that can activate the immune system for protection against various diseases. As carbohydrates can play important roles in immune recognition, they have been widely applied in vaccine development. Carbohydrate antigens have been investigated in vaccines against various pathogenic microbes and cancer. Polysaccharides such as dextran and β-glucan can serve as smart vaccine carriers for efficient antigen delivery to immune cells. Some glycolipids, such as galactosylceramide and monophosphoryl lipid A, are strong immune stimulators, which have been studied as vaccine adjuvants. In this review, we focus on the current advances in applying carbohydrates as vaccine delivery carriers and adjuvants. We will discuss the examples that involve chemical modifications of the carbohydrates for effective antigen delivery, as well as covalent antigen-carbohydrate conjugates for enhanced immune responses.

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Section: Introductionmentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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“…As a result, there have been myriad attempts to prepare vaccine constructs to raise effective and durable immune responses to TACAs. 4–13…”

Section: Introductionmentioning

confidence: 99%

“…10 It is thus not surprising that vaccine development against these antigens has been problematic; however, many strategies have met with success. The use of various delivery platforms 4,[14][15][16][17] , conjugations to immunogenic proteins (KLH, Tetanus toxin) 18 or peptide epitopes to generate T-cell help [19][20][21][22] , covalent conjugation to Toll-like receptor agonists, 6,18,20,23 the use of various adjuvants 24 and attachment to zwitterionic polysaccharides 25,26 have led to robust immune responses to carbohydrate structures and some have moved into clinical trials. However, none of these efforts have led to a truly effective, FDA approved therapy against any type of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…As a result, there have been myriad attempts to prepare vaccine constructs to raise effective and durable immune responses to TACAs. [4][5][6][7][8][9][10][11][12][13] TACAs are composed of self-molecules, and hence are innately weak immunogens; this makes them "tolerant" to robust immune responses. Carbohydrates are also T-cell independent epitopes and mobilization of that arm of the immune response is essential to eradicate any established tumor.…”

Section: Introductionmentioning

confidence: 99%

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A Stable Nano-Vaccine for the Targeted Delivery of Tumor-Associated Glycopeptide Antigens

2021

Preprint

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We have developed a novel antigen delivery system based on polysaccharide-coated gold nanoparticles (AuNPs) targeted to antigen presenting cells (APCs) expressing Dectin-1. AuNPs were synthesized de-novo using yeast-derived beta-1,3-glucans (B13Gs) as the reductant and passivating agent in a microwave-catalyzed procedure yielding highly uniform and serum-stable particles. These were further functionalized with both peptides and glycopeptides from the tandem repeat sequence of mucin 4 (MUC4), a glycoprotein overexpressed in pancreatic tumors. The glycosylated sequence contained the Thomsen-Friedenreich disaccharide, a pan-carcinoma, tumor-associated carbohydrate antigen which has been a traditional target for antitumor vaccine design. These motifs were prepared with a cathepsin D protease cleavage site (Gly-Phe-Leu-Gly), loaded on the B13Gs-coated particles and these constructs were examined for Dectin-1 binding, APC processing and presentation in a model in vitro system and for immune responses in mice. We showed that these particles elicit strong in vivo immune responses through the production of both high-titer antibodies and priming of antigen-recognizing T-cells by ELISPOT analysis. Further examination showed that a favorable antitumor balance of expressed cytokines was generated, with little or no expression of immunosuppressive Il-10. This system is modular in that any range of antigens can be conjugated to our particles and efficiently delivered to APCs expressing Dectin-1.

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“…[9][10][11] Additionally, glycoconjugates incorporating tumorassociated carbohydrate antigens have shown early promise as therapeutic cancer vaccines in clinical trials. 3,12 Despite these successes, glycans remain challenging vaccine targets. Polysaccharide and oligosaccharide antigens are often inherently poor immunogens because they lack peptide epitopes that can recruit CD4 T cells to the immune response.…”

Section: Introductionmentioning

confidence: 99%

Modular Polymer Antigens To Optimize Immunity

et al. 2019

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Subunit vaccines can have excellent safety profiles, but their ability to give rise to robust immune responses is often compromised. For glycan-based vaccines, insufficient understanding of B and T cell epitope combinations that yield optimal immune activation hinders optimization. To determine which antigen features promote desired IgG responses, we synthesized epitope-functionalized polymers using ring-opening metathesis polymerization (ROMP) and assessed the effect of B and T cell epitope loading. The most robust responses were induced by polymers with a high valency of B and T cell epitopes. Additionally, IgG responses were greater for polymers with T cell epitopes that are readily liberated upon endosomal processing. Combining these criteria, we used ROMP to generate a non-toxic, polymeric antigen that elicited stronger antibody responses than a comparable protein conjugate. These findings highlight principles for designing synthetic antigens that elicit strong IgG responses against inherently weak immune targets such as glycans.

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Recent advances in carbohydrate-based cancer vaccines

Cited by 32 publications

References 45 publications

Carbohydrate Conjugates in Vaccine Developments

Carbohydrate Conjugates in Vaccine Developments

A Stable Nano-Vaccine for the Targeted Delivery of Tumor-Associated Glycopeptide Antigens

Modular Polymer Antigens To Optimize Immunity

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