In addition to surgery, radiation therapy, and chemotherapy, there are high hopes for a fourth modality of cancer treatment: immunotherapy, which exploits the physiological immune system. Emerging immunotherapies that block immune checkpoints, including antibodies to CTLA-4, PD-1, PD-L1, and similar molecules, have been shown to have dramatic, long-term antitumor effects 1,2. Tasuku Honjo and James P. Allison were awarded the 2018 Nobel Prize in physiology for their research on these drugs. In cancer immunotherapy, identification of improved cancer-specific antigens is essential for higher effectiveness and lower side effects. Since Boon first identified the cancer-specific antigen for melanoma in 1991, many researchers throughout the world have sought new cancer antigens 3. Our research group identified glypican-3 (GPC3), a hepatocellular carcinoma specific antigen, in 2001. GPC3 has high cancer specificity and is an ideal target for cancer immunotherapy. This article is an overview of GPC3 and cancer immunotherapy targeting GPC3.
This is the first of a series of articles on bioinformatics resources for glycoscience research. This first article will give a brief introduction to background knowledge that would be useful to read the rest of the articles. In particular, a description of the commonly used text and symbolic nomenclature to represent glycans will be given, along with recommendations for which representation to use. This is followed by brief descriptions of the types of resources that will be explained in this series. Glycan-related web resources vary from databases to web services to web portals of integrated data. It is difficult to try to weed through this web of data, and so this article attempts to organize the information in a way that users can understand the current state of these resources. Note that although there is a section on “glycoconjugates” which covers not only glycoproteins, but also glycolipids, proteoglycans, GPI-anchors, etc., the current state of databases only covers glycoproteins in general. The other types of glycoconjugates are not forgotten, however, and will be the focus of future development.
Keratan sulfate, a glycan consisting of repeated disaccharides, is covalently bound to proteins. The repeating disaccharide units differ in sulfation pattern, and a disaccharide unit in which both 6-hydroxyls are sulfated is designated as L4. L4 has been shown to have anti-inflammatory effects, and in particular, it suppressed emphysema in chronic obstructive pulmonary disease (COPD) model mice. As to its action mechanisms, L4 is suggested to regulate the functions of immune cells through binding to a C-type lectin, Langerin, highly expressed in dendritic cells. We have synthesized chemical derivatives of L4 with higher affinity to Langerin, and are investigating their binding to Langerin, anti-inflammatory effects in COPD model mice, and mechanisms of actions.
