A Vision for Vaccines Built from Fully Synthetic Tumor-Associated Antigens: From the Laboratory to the Clinic

Wilson, Rebecca M.; Danishefsky, Samuel J.

doi:10.1021/ja405932r

Cited by 131 publications

(149 citation statements)

References 70 publications

(78 reference statements)

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“…The ideal targets can help identify tumor cells from normal cells explicitly, so that powerful and specific immune response can be elicited. Or else majorities of ravages of autoimmunity would introduce . As mentioned above, TACAs are supposed to be a promising kind of potential anticancer epitopes.…”

Section: Translating Tacas Into Cancer Vaccinesmentioning

confidence: 99%

“…Active immunotherapy trains the immune system to kill tumor cells through targeting tumor‐associated antigens, including immunostimulatory cytokine, immunomodulatory mAbs, pattern recognition receptor (PRR) agonist, and cancer vaccine . Among all these immunotherapies, cancer vaccine seems an ideal scheme, which not only can target therapy on tumor, but also can keep them from relapsing …”

Section: Introductionmentioning

confidence: 99%

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Carbohydrate‐based vaccines for oncotherapy

Wei

Wang

2018

Medicinal Research Reviews

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Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can differentiate the abnormal tissues from the healthy ones. Therefore, tumor-associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance. Different approaches have been developed to address these problems. In this review, we want to summarize the latest advances in TACAs based anticancer vaccines.

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Section: Translating Tacas Into Cancer Vaccinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Carbohydrate‐based vaccines for oncotherapy

Wei

Wang

2018

Medicinal Research Reviews

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“…5,6 In fact, neo-glycoproteins have been already developed 7,8 to obtain vaccine products of clinical relevance for the prevention of infective diseases 9 and have also been largely investigated as therapeutic anticancer vaccines. 10 In addition, the conjugation of antigenic peptides/proteins with synthetic immunogenic carbohydrates might strongly increase their biological activity by improving the peptide/protein antigen uptake targeting receptors of APC. 6,11 On the other hand, the glycosylation of antigenic peptides/proteins should exclude the amino acids involved in the epitopes to prevent a decrease or the loss of their biological activity.…”

Section: -3mentioning

confidence: 99%

Rational design, preparation and characterization of recombinant Ag85B variants and their glycoconjugates with T-cell antigenic activity againstMycobacterium tuberculosis

et al. 2018

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a Tuberculosis is the deadliest infectious disease in the world. The variable efficacy of the current treatments highlights the need for more effective agents against this disease. In the past few years, we focused on the investigation of antigenic glycoconjugates starting from recombinant Ag85B (rAg85B), a potent protein antigen from Mycobacterium tuberculosis. In this paper, structural modifications were rationally designed in order to obtain a rAg85B variant protein able to maintain its immunogenicity after glycosylation. Lysine residues involved in the main T-epitope sequences (namely, K30 and K282) have been substituted with arginine to prevent their glycosylation by a lysine-specific reactive linker. The effectiveness of the mutation strategy and the detailed structure of resulting neo-glycoconjugates have been studied by intact mass spectrometry, followed by peptide and glycopeptide mapping. The effect of K30R and K282R mutations on the T-cell activity of rAg85B has also been investigated with a preliminary immunological evaluation performed by enzyme-linked immunospotting on the different variant proteins and their glycosylation products. After glycosylation, the two variant proteins with an arginine in position 30 completely retain the original T-cell activity, thus representing adequate antigenic carriers for the development of efficient glycoconjugate vaccines against tuberculosis.

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“…The tumor-associated carbohydrate antigens are thus emerging as novel biomarkers for diagnosis and as attractive targets for cancer vaccines (Gaidzik et al, 2013; Wilson and Danishefsky, 2013). For example, MUC1, the type 1 mucin glycoproteins are present on most epithelial cells, which are often overexpressed in cancer cells and appended with truncated O-linked glycans (with only GalNAc, Galβ1, 3GalNAc, or sialylated GalNAc) instead the more extended large O-glycans found in normal cells.…”

Section: Synthesis Of Mucin Glycopeptides As Anti-cancer Vaccinesmentioning

confidence: 99%

Chemical and Chemoenzymatic Synthesis of Glycoproteins for Deciphering Functions

Wang

Amin

2014

Chemistry & Biology

149

144

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Summary Glycoproteins are an important class of biomolecules involved in a number of biological recognition processes. However, natural and recombinant glycoproteins are usually produced as mixtures of glycoforms that differ in the structures of the pendent glycans, which are difficult to separate in pure glycoforms. As a result, synthetic homogeneous glycopeptides and glycoproteins have become indispensable probes for detailed structural and functional studies. A number of elegant chemical and biological strategies have been developed for synthetic construction of tailor-made, full-size glycoproteins to address specific biological problems. In this review, we highlight recent advances in chemical and chemoenzymatic synthesis of homogeneous glycoproteins. Selected examples are given to demonstrate the applications of tailor-made, glycan-defined glycoproteins for deciphering glycosylation functions.

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A Vision for Vaccines Built from Fully Synthetic Tumor-Associated Antigens: From the Laboratory to the Clinic

Cited by 131 publications

References 70 publications

Carbohydrate‐based vaccines for oncotherapy

Carbohydrate‐based vaccines for oncotherapy

Rational design, preparation and characterization of recombinant Ag85B variants and their glycoconjugates with T-cell antigenic activity againstMycobacterium tuberculosis

Chemical and Chemoenzymatic Synthesis of Glycoproteins for Deciphering Functions

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