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Expert Opin Ther Targets. 2015 Mar;19(3):349-62. doi: 10.1517/14728222.2014.986459. Epub 2015 Jan 20.

Disialoganglioside GD2 as a therapeutic target for human diseases.

Author information

1
Memorial Sloan Kettering Cancer Center, Department of Pediatrics , 1275 York Avenue, New York, NY 10065 , USA +1 646 888 2313 ; +1 631 422 0452 ; cheungn@mskcc.org.

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:

GD2; cancer; immunotherapy; mAb

PMID:
25604432
DOI:
10.1517/14728222.2014.986459
[Indexed for MEDLINE]

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