GD2

Not to be confused with GD Graphics Library.
GD2
Names
IUPAC name
(2R,4R,5S,6S)-2-[3-[(2S,3S,4R,6S)-6-[(2S,3R,4R,5S,6R)-5-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(E)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3-amino-6-carboxy-4-hydroxyoxan-2-yl]-2,3-dihydroxypropoxy]-5-amino-4-hydroxy-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Other names
Ganglioside G2
Identifiers
3D model (JSmol)
UNII
  • InChI=1S/C74H134N4O32/c1-4-6-8-10-12-14-16-18-19-21-23-25-27-29-31-33-52(89)78-43(44(84)32-30-28-26-24-22-20-17-15-13-11-9-7-5-2)40-101-69-61(95)60(94)63(50(38-81)104-69)106-70-62(96)67(64(51(39-82)105-70)107-68-55(77-42(3)83)59(93)58(92)49(37-80)103-68)110-74(72(99)100)35-46(86)54(76)66(109-74)57(91)48(88)41-102-73(71(97)98)34-45(85)53(75)65(108-73)56(90)47(87)36-79/h30,32,43-51,53-70,79-82,84-88,90-96H,4-29,31,33-41,75-76H2,1-3H3,(H,77,83)(H,78,89)(H,97,98)(H,99,100)/b32-30+/t43?,44?,45-,46-,47?,48?,49-,50-,51-,53+,54+,55-,56?,57?,58+,59-,60-,61-,62-,63-,64+,65+,66+,67-,68+,69-,70+,73-,74+/m1/s1
    Key: FFILOTSTFMXQJC-QCFYAKGBSA-N
  • CCCCCCCCCCCCCCCCCC(=O)NC(CO[C@H]1[C@@H]([C@H]([C@@H]([C@H](O1)CO)O[C@H]2[C@@H]([C@H]([C@H]([C@H](O2)CO)O[C@H]3[C@@H]([C@H]([C@H]([C@H](O3)CO)O)O)NC(=O)C)O[C@@]4(C[C@H]([C@@H]([C@H](O4)C(C(CO[C@@]5(C[C@H]([C@@H]([C@H](O5)C(C(CO)O)O)N)O)C(=O)O)O)O)N)O)C(=O)O)O)O)O)C(/C=C/CCCCCCCCCCCCC)O
Properties
C74H134N4O32
Molar mass 1591.882 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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GD2 is a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues, principally to the cerebellum and peripheral nerves in humans.

The relatively tumor-specific expression of GD2 makes it a suitable target for immunotherapy with monoclonal antibodies or with artificial T cell receptors, Recently, GD2 has been explored as a therapeutic target in neuroblastoma using genetically engineered M13 bacteriophages. In this approach, the phages were modified to display an anti-GD2 single-chain variable fragment (scFv) derived from the FDA-approved antibody Dinutuximab on their pIII coat protein. These engineered phages were further loaded with hundreds of photosensitizer molecules to enable selective delivery to GD2-positive neuroblastoma cells. Upon activation by laser light or ultrasound, the photosensitizers triggered precise and targeted killing of GD2-expressing tumor cells both in vitro and in vivo.[1][2] An example of such antibodies is hu14.18K322A, a monoclonal antibody. This anti-GD2 antibody is currently undergoing a phase II clinical trial in the treatment of previously untreated high risk neuroblastoma given alongside combination chemotherapy prior to stem cell transplant and radiation therapy.[3] A prior phase I clinical trial for patients with refractory or recurrent neuroblastoma designed to decrease toxicity found safe dosage amounts and determined that common toxicities, particularly pain, could be well managed.[4] The chimeric (murine-human) anti-GD2 monoclonal antibody ch14.18 is FDA-approved for the treatment of pediatric patients with high-risk neuroblastoma and has been studied in patients with other GD2-expressing tumors.[5]

See also

References

  1. ^ Zadran, Suleman Khan; Facchinello, Nicola; De Rosa, Piergiuseppe; Saporetti, Roberto; Costantini, Paolo Emidio; Ulfo, Luca; Nigro, Michela et al. (2025). "Systematic Targeting of GD2‐Positive Neuroblastoma Tumors With a Photooncolytic Phage Nanovector Platform." Advanced Science. 12: e15356. https://doi.org/10.1002/advs.202415356 .
  2. ^ Wierzbicki, Andrzej; Gil, Margaret; Ciesielski, Michael; Fenstermaker, Robert A.; Kaneko, Yutaro; Rokita, Hanna; Lau, Joseph T.; Kozbor, Danuta (2008). "Immunization with a Mimotope of GD2 Ganglioside Induces CD8+ T Cells That Recognize Cell Adhesion Molecules on Tumor Cells". Journal of Immunology. 181 (9): 6644–6653. doi:10.4049/jimmunol.181.9.6644. PMC 2730120. PMID 18941255.
  3. ^ "Clinical trials using anti-GD2 monoclonal antibody hu14.18K322A". National Cancer Institute. Retrieved April 20, 2018.
  4. ^ Navid F, et al. (May 2014). "Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma". Journal of Clinical Oncology. 32 (14): 1445–52. doi:10.1200/JCO.2013.50.4423. PMC 4017710. PMID 24711551.
  5. ^ Bassel N, Cengiz I, Owonikoko TK (July 2020). "Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy". Frontiers in Oncology. 10: 1000. doi:10.3389/fonc.2020.01000. ISSN 2234-943X. PMC 7358363. PMID 32733795.

Further reading

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