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Targeting glycosphingolipids for cancer immunotherapy
John Yu1,2, Jung-Tung Hung1, Sheng-Hung Wang1
1Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan.
Abstract:
Aberrant expression of glycosphingolipids (GSLs) is a unique feature of cancer and stromal cells in tumor microenvironments. Although the impact of GSLs on tumor progression remains largely unclear, anticancer immunotherapies directed against GSLs are attracting growing attention. Here, we focus on GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and Globo H ceramide (GHCer), the most prevalent cancer-associated GSL overexpressed in a variety of epithelial cancers. We first summarize recent advances on our understanding of GD2 and GHCer biology and then discuss the clinical development of the first immunotherapeutic agent targeting a glycolipid, the GD2-specific antibody dinutuximab, its approved indications, and new strategies to improve its efficacy for neuroblastoma. Next, we review ongoing clinical trials on Globo H-targeted immunotherapeutics. We end with highlighting how these studies provide sound scientific rationales for targeting GSLs in cancer and may facilitate a rational design of new GSL-targeted anticancer therapeutics.
Insights
Aberrant glycosphingolipids (GSLs) are hallmarks of cancer. This review explores GD2 and Globo H ceramide (GHCer) GSLs, discussing immunotherapies like dinutuximab and emerging Globo H treatments for enhanced cancer therapy.
Area of Science:
- Oncology
- Immunology
- Glycobiology
Background:
- Aberrant expression of glycosphingolipids (GSLs) is a characteristic feature of cancer cells and the tumor microenvironment.
- The precise role of GSLs in tumor progression is not fully understood, but GSL-targeted immunotherapies are gaining traction.
- GD2, a disialoganglioside, is found in neuroectodermal tumors, while Globo H ceramide (GHCer) is prevalent in epithelial cancers.
Purpose of the Study:
- To review the biology of GD2 and GHCer GSLs in cancer.
- To discuss the clinical development and efficacy of GD2-targeted immunotherapeutics, such as dinutuximab.
- To examine ongoing clinical trials for Globo H-targeted immunotherapies and their potential for novel cancer therapeutics.
Main Methods:
- Literature review summarizing recent advances in GD2 and GHCer biology.
- Analysis of clinical development of dinutuximab, a GD2-specific antibody.
- Review of ongoing clinical trials for Globo H-targeted immunotherapeutics.
Main Results:
- Dinutuximab is an approved GD2-targeted immunotherapeutic agent for neuroblastoma, with ongoing strategies to enhance its efficacy.
- Several clinical trials are evaluating Globo H-targeted immunotherapeutics for various epithelial cancers.
- These studies provide a strong scientific basis for targeting GSLs in cancer treatment.
Conclusions:
- Targeting GSLs like GD2 and GHCer represents a promising strategy in cancer immunotherapy.
- The development of GSL-specific antibodies and other immunotherapeutics offers new avenues for cancer treatment.
- Further research and clinical trials are essential for optimizing GSL-targeted therapies and designing novel anticancer agents.
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