Targeting glycosphingolipids for cancer immunotherapy

Yu, John; Hung, Jung‐Tung; Wang, Sheng-Hung; Cheng, Jing-Yan; Yu, Alice L.

doi:10.1002/1873-3468.13917

Cited by 41 publications

(23 citation statements)

References 125 publications

(191 reference statements)

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“…Globo H is a prevalent cancer-associated glycosphingolipid and is overexpressed in many cancers of epithelial origins (e.g., breast, ovary, uterus, prostate, lung, colon, and liver cancers) [ 26 ]. Currently, there are several ongoing clinical trials on immunotherapies targeting globo H. Immunohistochemistry studies have demonstrated the presence of Globo H in 33% of MTCs, but not in normal thyroidea or benign thyroid lesions [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

Säljö

Thornell

Jin

et al. 2021

IJMS

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Medullary thyroid carcinoma (MTC) accounts for only 1–2% of thyroid cancers; however, metastatic MTC is a mortal disease with no cure. In this study, glycosphingolipids were isolated from human MTCs and characterized by mass spectrometry and binding of carbohydrate recognizing ligands. The tissue distribution of selected compounds was investigated by immunohistochemistry. The amount of acid glycosphingolipids in the MTCs was higher than in the normal thyroid glands. The major acid glycosphingolipid was the GD3 ganglioside. Sulfatide and the gangliosides GM3 and GD1a were also present. The majority of the complex non-acid glycosphingolipids had type 2 (Galβ4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Lex, H type 2 and x2 pentaosylceramides, the Ley and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (GalαGalβ4Glc) core, i.e., globotriaosylceramide, globotetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Immunohistochemistry demonstrated an extensive expression av Ley in the MTC cells and also a variable intensity and prevalence of Globo H and Lex. One individual with multiple endocrine neoplasia type 2B expressed the Forssman determinant, which is rarely found in humans. This study of human MTC glycosphingolipids identifies glycans that could serve as potential tumor-specific markers.

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Section: Discussionmentioning

confidence: 99%

Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

Säljö

Thornell

Jin

et al. 2021

IJMS

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“…Due to the various biological functions, sphingolipids and their derivatives have been studied for therapeutic applications of diverse diseases such as cancer, and autoimmune diseases ( Table 4 ). In cancer immunotherapy, targeting specific types of glycosphingolipids has been shown to modulate the immune microenvironments of tumors ( Yu et al ., 2020 ). Safingol and fingolimod are examples of sphinolipid analogues for clinical applications ( Choi and Song, 2020 ).…”

Section: Sphingolipidsmentioning

confidence: 99%

Bioactive Lipids and Their Derivatives in Biomedical Applications

Park

Choi

Kim

et al. 2021

Biomolecules & Therapeutics

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Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

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“…Generating high affinity binding ligands against GSLs is a notoriously difficult task due to the high structural flexibility of these molecules. An exception is the anti-GD2 antibody dinutuximab, which entered the market for the treatment of high-risk neuroblastoma patients [ 94 ].…”

Section: Therapeutic Deliverymentioning

confidence: 99%

The Cellular and Chemical Biology of Endocytic Trafficking and Intracellular Delivery—The GL–Lect Hypothesis

Johannes

2021

Molecules

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Lipid membranes are common to all forms of life. While being stable barriers that delimitate the cell as the fundamental organismal unit, biological membranes are highly dynamic by allowing for lateral diffusion, transbilayer passage via selective channels, and in eukaryotic cells for endocytic uptake through the formation of membrane bound vesicular or tubular carriers. Two of the most abundant fundamental fabrics of membranes—lipids and complex sugars—are produced through elaborate chains of biosynthetic enzymes, which makes it difficult to study them by conventional reverse genetics. This review illustrates how organic synthesis provides access to uncharted areas of membrane glycobiology research and its application to biomedicine. For this Special Issue on Chemical Biology Research in France, focus will be placed on synthetic approaches (i) to study endocytic functions of glycosylated proteins and lipids according to the GlycoLipid–Lectin (GL–Lect) hypothesis, notably that of Shiga toxin; (ii) to mechanistically dissect its endocytosis and intracellular trafficking with small molecule; and (iii) to devise intracellular delivery strategies for immunotherapy and tumor targeting. It will be pointed out how the chemical biologist’s view on lipids, sugars, and proteins synergizes with biophysics and modeling to “look” into the membrane for atomistic scale insights on molecular rearrangements that drive the biogenesis of endocytic carriers in processes of clathrin-independent endocytosis.

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Targeting glycosphingolipids for cancer immunotherapy

Cited by 41 publications

References 125 publications

Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

Bioactive Lipids and Their Derivatives in Biomedical Applications

The Cellular and Chemical Biology of Endocytic Trafficking and Intracellular Delivery—The GL–Lect Hypothesis

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