Disialoganglioside GD2 as a therapeutic target for human diseases

Abstract

Introduction: Ganglioside GD2 is found in vertebrates and invertebrates, overexpressed among pediatric and adult solid tumors, including neuroblastoma, glioma, retinoblastoma, Ewing’s family of tumors, rhabdomyosarcoma, osteosarcoma, leiomyosarcoma, liposarcoma, fibrosarcoma, small cell lung cancer and melanoma. It is also found on stem cells, neurons, some nerve fibers and basal layer of the skin.

Areas covered: GD2 provides a promising clinical target for radiolabeled antibodies, bispecific antibodies, chimeric antigen receptor (CAR)-modified T cells, drug conjugates, nanoparticles and vaccines. Here, we review its biochemistry, normal physiology, role in tumorigenesis, important characteristics as a target, as well as anti-GD2-targeted strategies.

Expert opinion: Bridging the knowledge gaps in understanding the interactions of GD2 with signaling molecules within the glycosynapses, and the regulation of its cellular expression should improve therapeutic strategies targeting this ganglioside. In addition to anti-GD2 IgG mAbs, their drug conjugates, radiolabeled forms especially when genetically engineered to improve therapeutic index and novel bispecific forms or CARs to retarget T-cells are promising candidates for treating metastatic cancers.

Keywords:

• cancer
• GD2
• immunotherapy
• mAb

Acknowledgement

We want to thank Irene Y Cheung, Mahiuddin Ahmed, and Joseph Olechnowicz for their valuable advice and suggestions.

Declaration of interest

The authors were supported by Grants from the Department of Defense (PR111043), Enid A Haupt Endowed Chair, Kids Walk for Kids with Cancer NYC, Katie’s Find a Cure foundation, Catie Hoch Foundation and the Robert Steel Foundation. NK Cheung was named as an inventor on patents filed by MSKCC on beta-glucan, 5F11, hu3F8, 8H9 and hu8H9. Beta-glucan was licensed by MSKCC to Biotec Pharmacon. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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