Targeting Tn-Antigen-Positive Human Tumors with a Recombinant Human Macrophage Galactose C-Type Lectin

Bulteau, Francois Bulteau; Thépaut, Michel; Henry, Maxime; Hurbin, Amandine; Vanwonterghem, Laetitia; Vivès, Corinne; Roy, Aline Le; Ebel, Christine; Renaudet, Olivier; Fieschi, Franck; Coll, Jean‐Luc

doi:10.1021/acs.molpharmaceut.1c00744

Cited by 17 publications

(19 citation statements)

References 47 publications

(66 reference statements)

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“…DC-SIGN Biot-ECD and MGL Biot-ECD, used in these SPR measurements, were overexpressed and purified according to previously published protocol [ 17 , 18 ]. A surface plasmon resonance experiment was performed on a T200 instrument.…”

Section: Methodsmentioning

confidence: 99%

Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses

et al. 2022

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Virus-like particles constitute versatile vectors that can be used as vaccine platforms in many fields from infectiology and more recently to oncology. We previously designed non-infectious adenovirus-inspired 60-mer dodecahedric virus-like particles named ADDomers displaying on their surface either a short epitope or a large tumor/viral antigen. In this work, we explored for the first time the immunogenicity of ADDomers exhibiting melanoma-derived tumor antigen/epitope and their impact on the features of human dendritic cell (DC) subsets. We first demonstrated that ADDomers displaying tumor epitope/antigen elicit a strong immune-stimulating potential of human DC subsets (cDC2s, cDC1s, pDCs), which were able to internalize and cross-present tumor antigen, and subsequently cross-prime antigen-specific T-cell responses. To further limit off-target effects and enhance DC targeting, we engineered specific motifs to de-target epithelial cells and improve DCs’ addressing. The improved engineered platform making it possible to display large antigen represents a tool to overcome the barrier of immune allele restriction, broadening the immune response, and paving the way to its potential utilization in humans as an off-the-shelf vaccine.

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Section: Methodsmentioning

confidence: 99%

Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses

et al. 2022

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“…In this context, the immune cells may elicit self-immunity under some conditions [159]. Among the unusual glycans carried by oncofetal proteins, Tn sialyl Tn antigens stand out [160,161]. Although many papers have demonstrated the importance of studying the immunobiological effects induced by the sialyl Tn antigen [162][163][164][165], in this last section of the article, we deal only with the Tn antigen, which is the simplest possible amino acid-carbohydrate glycoconjugate and Thanks to advances in the field of glycoimmunology, today we know many siglec genes and binding specificities are quickly evolving among primates, with crucial extant polymorphisms in human populations that may impact vulnerability to infection-associated disorders [135].…”

Section: Oncofetal Antigens As Modulators Of the Immune Responsementioning

confidence: 99%

“…In this context, the immune cells may elicit self-immunity under some conditions [ 159 ]. Among the unusual glycans carried by oncofetal proteins, Tn sialyl Tn antigens stand out [ 160 , 161 ]. Although many papers have demonstrated the importance of studying the immunobiological effects induced by the sialyl Tn antigen [ 162 , 163 , 164 , 165 ], in this last section of the article, we deal only with the Tn antigen, which is the simplest possible amino acid–carbohydrate glycoconjugate and comprises a 2-deoxy-2-acetamido-d-galactose (GalNAc) α- O -linked to either serine or threonine residues in a polypeptide chain [ 166 ].…”

Section: Oncofetal Antigens As Modulators Of the Immune Responsementioning

confidence: 99%

The Blessed Union of Glycobiology and Immunology: A Marriage That Worked

et al. 2023

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In this article, we discuss the main aspects regarding the recognition of cell surface glycoconjugates and the immunomodulation of responses against the progression of certain pathologies, such as cancer and infectious diseases. In the first part, we talk about different aspects of glycoconjugates and delve deeper into the importance of N-glycans in cancer immunotherapy. Then, we describe two important lectin families that have been very well studied in the last 20 years. Examples include the sialic acid-binding immunoglobulin (Ig)-like lectins (siglecs), and galectins. Finally, we discuss a topic that needs to be better addressed in the field of glycoimmunology: the impact of oncofetal antigens on the cells of the immune system. New findings in this area are of great importance for advancement, especially in the field of oncology, since it is already known that cellular interactions mediated by carbohydrate–carbohydrate and/or carbohydrate proteins are able to modulate the progression of different types of cancer in events that compromise the functionality of the immune responses.

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“…24 Lectins such as the human macrophage galactose lectin (MGL) also bind to these TACAs and particularly to Tn antigen, which makes this protein useful for therapeutic applications. 25 In this Account, we focus on enzymes, antibodies, and lectins (Figure 1) that recognize the GalNAc moiety in glycopeptides. To this end, we will show examples from our laboratories of 3D structures of these proteins in complex with glycopeptides determined by X-ray crystallography or NMR experiments.…”

Section: ■ Introductionmentioning

confidence: 99%

Molecular Recognition of GalNAc in Mucin-Type O-Glycosylation

et al. 2023

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Conspectus N-Acetylgalactosamine (GalNAc)-type O-glycosylation is an essential posttranslational modification (PTM) that plays fundamental roles in biology. Malfunction of this PTM is exemplified by the presence of truncated O-glycans in cancer. For instance, the glycoprotein MUC1 is overexpressed in many tumor tissues and tends to carry simple oligosaccharides that allow for the presentation of different tumor-associated antigens, such as the Tn or sTn antigens (GalNAc-α-1-O-Thr/Ser and Neu5Acα2-6GalNAcα1-O-Ser/Thr, respectively). In other cases, such as tumoral calcinosis associated with O-glycosylation of the fibroblast growth factor 23, O-glycans are absent or less abundant. Significant progress has been made in determining the three-dimensional structures of biomolecules that recognize GalNAc, such as antibodies, lectins, mucinases, GalNAc-transferases, and other glycosyltransferases. Analysis of the complexes between these entities and GalNAc-containing glycopeptides, in most cases derived from crystallographic or NMR analysis, provides an understanding of the key structural elements that control molecular recognition of these glycopeptides. Here, we describe and compare the binding sites of these proteins in detail, focusing on how the GalNAc moieties interact selectively with them. We also summarize the differences and similarities in GalNAc recognition. In general, the recognition of GalNAc-containing glycopeptides is determined by hydrogen bonds between hydroxyl groups and the N-acetyl group of GalNAc with proteins, as well as CH-π contacts in which the hydrophobic α-face of the sugar and the methyl group of NHAc can be involved. The latter interaction usually provides the basis for selectivity. It is worth noting that binding of these glycopeptides depends primarily on recognition of the sugar moiety, with some exceptions such as a few anti-MUC1 antibodies that primarily recognize the peptide backbone and use the sugar to facilitate shape complementarity or to establish a limited number of interactions with the protein. Focusing specifically on the GalNAc moiety, we can observe that there is some degeneracy of interactions within the same protein families, likely due to substrate flexibility. However, when all studied proteins are considered together, despite the commonalities within each protein family, no pattern can be discerned between the different families, apart from the presence of common residues such as Tyr, His, or Asp, which are responsible for hydrogen bonds. The lack of a pattern can be anticipated, given the diverse functions of mucinases, glycosyltransferases, antibodies, and lectins. Finally, it is important to point out that the conformational differences observed in solution in glycopeptides bearing GalNAc-α-1-O-Ser or GalNAc-α-1-O-Thr also can be found in the bound state. This unique characteristic is exploited, for instance, by the enzyme C1GalT1 to broadly glycosylate both acceptor substrates. The findings summarized in this review may contribute to the rational structure-guided ...

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Targeting Tn-Antigen-Positive Human Tumors with a Recombinant Human Macrophage Galactose C-Type Lectin

Cited by 17 publications

References 47 publications

Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses

Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses

The Blessed Union of Glycobiology and Immunology: A Marriage That Worked

Molecular Recognition of GalNAc in Mucin-Type O-Glycosylation

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