Sialyl-Tn in Cancer: (How) Did We Miss the Target?

Julien, Sylvain; Videira, Paula A.; Delannoy, Philippe

doi:10.3390/biom2040435

Cited by 143 publications

(178 citation statements)

References 144 publications

(243 reference statements)

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“…Glycosylation of IgG is known to play a role in tumour immune surveillance and is being investigated as a diagnostic marker in several cancer types [152–155]. Targeting altered glycosylation using anticancer vaccines that target tumour associated antigens is an appealing option for cancer treatment [156, 157]. …”

Section: Avoiding Immune Destructionmentioning

confidence: 99%

Hallmarks of glycosylation in cancer

2016

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Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a ‘hallmark of cancer’ but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark.

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Section: Avoiding Immune Destructionmentioning

confidence: 99%

Hallmarks of glycosylation in cancer

2016

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“…The influence of ST6GalNAcs on cancer progression is most widely-recognized through their regulation of Tn and sTn antigens, which are considered biomarkers of cancer (3, 17, 41–43). Either elevated ST6GalNAc1 levels or compromised synthesis of T antigen via mutant Cosmic can raise sTn levels on cancer cells – a direct correlate of progression and poor prognosis (42–44).…”

Section: B α26 Siaylation Of O-glycans and Its Impact On Cancer Promentioning

confidence: 99%

Galectin-Binding O-Glycosylations as Regulators of Malignancy

Dimitroff

2015

Cancer Research

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Cancer cells commonly display aberrant surface glycans and related glycoconjugate scaffolds. Compared with their normal counterparts, cancer cell glycans are variably produced and often structurally distinct, serving as biomarkers of cancer progression or as functional entities to malignancy. The glycan signature of a cancer cell is created by the collaborative activities of glycosyltransferases, glycosidases, nucleotide-sugar transporters, sulfotransferases and glycan-bearing protein/lipid scaffolds. In a coordinated fashion, these factors regulate the synthesis of cancer cell glycans and thus are considered correlates of cancer cell behavior. Functionally, cancer cell glycans can serve as binding targets for endogenous lectin effectors, such as C-type selectins and S-type galectins. There has been a recent surge of important observations on the role of glycosytransferases, specifically α2,6 sialyltransferases, in regulating the length and lectin-binding features of serine/threonine (O)-glycans found on cancer cells. The capping activity of O-glycan-specific α2,6 sialyltransferases, in particular, has been found to regulate cancer growth and metastasis in a galectin-dependent manner. These findings highlight the functional importance of cancer cell O-glycans and related galectin-binding features in the virulent activity of cancer and raise the prospect of targeting cancer cell glycans as effective anti-cancer therapeutics.

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“…Glycosylation of proteins is one of the most abundant and diverse post-translational modifications, with more than half of all human proteins estimated to be glycosylated 2 . Aberrant glycosylation has been implicated in an array of human diseases and is a common feature of cancer cells 3,4 . One altered glycosylation pathway associated with malignancy is O-glycan biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity

Prendergast

Silva

Eavarone

et al. 2017

mAbs

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Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

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Sialyl-Tn in Cancer: (How) Did We Miss the Target?

Cited by 143 publications

References 144 publications

Hallmarks of glycosylation in cancer

Hallmarks of glycosylation in cancer

Galectin-Binding O-Glycosylations as Regulators of Malignancy

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity

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