Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 19, Issue 3, Pages 349-362Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2014.986459
Keywords
cancer; GD2; immunotherapy; mAb
Categories
Funding
- 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
- Robert Steel Foundation
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Introduction: Ganglioside GD2 is found in vertebrates and invertebrates, over-expressed 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.
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