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'''GD2''' is a [[disialoganglioside]] expressed on tumors of [[neuroectoderm]]al origin, including human [[neuroblastoma]] and [[melanoma]], with highly restricted expression on normal tissues, principally to the [[cerebellum]] and [[peripheral nerves]] in humans.
'''GD2''' is a [[disialoganglioside]] expressed on tumors of [[neuroectoderm]]al 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 receptor]]s.<ref>{{Cite journal |author1=Wierzbicki, Andrzej |author2=Gil, Margaret |author3=Ciesielski, Michael |author4=Fenstermaker, Robert A. |author5=Kaneko, Yutaro |author6=Rokita, Hanna |author7=Lau, Joseph T. |author8=Kozbor, Danuta | title = Immunization with a Mimotope of GD2 Ganglioside Induces CD8+ T Cells That Recognize Cell Adhesion Molecules on Tumor Cells | journal = Journal of Immunology | year = 2008 | volume = 181 | issue = 9 | pages = 6644–6653 | pmid=18941255 | pmc = 2730120 | doi=10.4049/jimmunol.181.9.6644}}</ref> 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]].<ref>{{cite web |url=https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/anti-gd2-monoclonal-antibody-hu1418k322a |title=Clinical trials using anti-GD2 monoclonal antibody hu14.18K322A |website=National Cancer Institute |access-date=April 20, 2018}}</ref> 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.<ref>{{cite journal |vauthors= Navid F, et al. |date= May 2014 |title= Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma |journal= Journal of Clinical Oncology|volume= 32 |issue= 14 |pages= 1445–52 |doi= 10.1200/JCO.2013.50.4423|pmc= 4017710 |pmid=24711551}}</ref> 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.<ref>{{cite journal |vauthors= Bassel N, Cengiz I, Owonikoko TK |date= July 2020 |title= Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy |journal= Frontiers in Oncology|volume= 10 |year= 2020 |pages=1000 |doi=10.3389/fonc.2020.01000 |pmid= 32733795 |pmc= 7358363 |issn=2234-943X|doi-access= free }}</ref>
The relatively tumor-specific expression of GD2 makes it a suitable target for [[immunotherapy]] with monoclonal antibodies or with artificial [[T cell receptor]]s.<ref>{{Cite journal |author1=Wierzbicki, Andrzej |author2=Gil, Margaret |author3=Ciesielski, Michael |author4=Fenstermaker, Robert A. |author5=Kaneko, Yutaro |author6=Rokita, Hanna |author7=Lau, Joseph T. |author8=Kozbor, Danuta | title = Immunization with a Mimotope of GD2 Ganglioside Induces CD8+ T Cells That Recognize Cell Adhesion Molecules on Tumor Cells | journal = Journal of Immunology | year = 2008 | volume = 181 | issue = 9 | pages = 6644–6653 | pmid=18941255 | pmc = 2730120 | doi=10.4049/jimmunol.181.9.6644}}</ref> 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]].<ref>{{cite web |url=https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/anti-gd2-monoclonal-antibody-hu1418k322a |title=Clinical trials using anti-GD2 monoclonal antibody hu14.18K322A |website=National Cancer Institute |access-date=April 20, 2018}}</ref> 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.<ref>{{cite journal |vauthors= Navid F, et al. |date= May 2014 |title= Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma |journal= Journal of Clinical Oncology|volume= 32 |issue= 14 |pages= 1445–52 |doi= 10.1200/JCO.2013.50.4423|pmc= 4017710 |pmid=24711551}}</ref> 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.<ref>{{cite journal |vauthors= Bassel N, Cengiz I, Owonikoko TK |date= July 2020 |title= Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy |journal= Frontiers in Oncology|volume= 10 |pages=1000 |doi=10.3389/fonc.2020.01000 |pmid= 32733795 |pmc= 7358363 |issn=2234-943X|doi-access= free }}</ref>


==See also==
==See also==
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==References==
==References==
{{reflist}}
{{reflist}}
2. Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. Ahmed M, Cheung NK. FEBS Lett. 2014 Jan 21;588(2):288-97


==Further Reading==
3. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Cheung NK, Dyer MA. Nat Rev Cancer. 2013 Jun;13(6):397-411
{{refbegin|2}}
*{{cite journal | vauthors = Ahmed M, Cheung NK | title = Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy | journal = FEBS Lett | volume = 588 | issue = 2 | pages = 288–97 | date = January 2014 | pmid = 24295643 | doi = 10.1016/j.febslet.2013.11.030 }}


*{{cite journal | vauthors = Cheung NK, Dyer MA | title = Neuroblastoma: developmental biology, cancer genomics and immunotherapy | journal = Nat Rev Cancer | volume = 13 | issue = 6 | pages = 397–411 | date = June 2013 | pmid = 23702928 | pmc = 4386662 | doi = 10.1038/nrc3526 }}
⚫
4. Sarkar T. R., Battula VL, Werden SJ, Vijay GV, Ramirez-Pea EQ, Taube JH, Chang JT, Miura N, Porter W, Sphyris N, Andreeff M, Mani SA. GD3 synthase regulates epithelial- mesenchymal transition and metastasis in breast cancer. Oncogene. 2015 Jun 4;34(23):2958- 67.


⚫
*{{cite journal | vauthors = Sarkar TR, Battula VL, Werden SJ, Vijay GV, Ramirez-Peña EQ, Taube JH, Chang JT, Miura N, Porter W, Sphyris N, Andreeff M, Mani SA | title = GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer | journal = Oncogene | volume = 34 | issue = 23 | pages = 2958–67 | date = June 2015 | pmid = 25109336 | pmc = 4324395 | doi = 10.1038/onc.2014.245 }}
{{refend}}
{{Sphingolipids}}
{{Sphingolipids}}


Revision as of 21:01, 6 November 2022

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
  • 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).
checkY verify (what is checkY☒N ?)

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.[1] 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.[2] 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.[3] 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.[4]

See also

References

  1. ^ 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.
  2. ^ "Clinical trials using anti-GD2 monoclonal antibody hu14.18K322A". National Cancer Institute. Retrieved April 20, 2018.
  3. ^ 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.
  4. ^ 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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