GD2 (disialoganglioside)
GD2 is a sugar-fat molecule on the surface of neuroblastoma cells (and some other childhood and adult tumours) with almost none on normal tissue except nerves, which is why anti-GD2 drugs cause pain.
Disialoganglioside GD2 is expressed at high density on nearly all neuroblastomas, most osteosarcomas and melanomas, and diffuse midline gliomas, with normal expression restricted to peripheral nerves, melanocytes and CNS. Anti-GD2 antibodies (dinutuximab, dinutuximab beta, naxitamab) improved high-risk neuroblastoma survival; GD2 CAR-T (GD2-CART01, Italian phase 1/2) gives durable complete responses in relapsed disease and shows activity in diffuse midline glioma (Stanford). Neuropathic pain from nerve GD2 binding is the class toxicity.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · GD2 is a sugar-fat molecule on the surface of neuroblastoma cells (and some other childhood and adult tumours) with almost none on normal tissue except nerves, which is why anti-GD2 drugs cause pain.
- 1 · What it is
GD2 is a sugar-fat molecule on the surface of neuroblastoma cells (and some other childhood and adult tumours) with almost none on normal tissue except nerves, which is why anti-GD2 drugs cause pain.
- 2 · What goes wrong in cancer
Glycosphingolipid synthesised by GD2 synthase (B4GALNT1); not internalised efficiently, so antibodies act by ADCC/CDC rather than as ADC carriers.
- 3 · How drugs use it
2 products aim at GD2 (disialoganglioside): antibodies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Biology
Glycosphingolipid synthesised by GD2 synthase (B4GALNT1); not internalised efficiently, so antibodies act by ADCC/CDC rather than as ADC carriers.
- Neuroblastoma (~100%)
- Osteosarcoma
- Melanoma
- Diffuse midline glioma / DIPG
- Small-cell lung cancer (subset)
- Ewing sarcoma (subset)
The antibody that raised cure rates in high-risk childhood neuroblastoma by about 20 points when given after transplant with immune boosters and retinoid.
Naxitamab is a humanised anti-GD2 antibody from Memorial Sloan Kettering, given as an outpatient with GM-CSF for relapsed neuroblastoma in bone or marrow.
Latest papers
topQuery for this target: (TITLE:"GD2" OR ABSTRACT:"GD2" OR TITLE:"disialoganglioside" OR ABSTRACT:"disialoganglioside" OR TITLE:"GD2 B4GALNT1 product" OR ABSTRACT:"GD2 B4GALNT1 product") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about GD2 (disialoganglioside), not a curated reading list.
Pages like this
not linked directly; found by shared links- InstitutionChildren's Oncology Group (COG)
Shares COG ANBL0032, Alice L. Yu, Julie R. Park, University of Wisconsin Carbone Cancer Center.
- TechnologyArmoured, logic-gated & next-gen CARs
Shares GD2 CAR-T as consolidation in high-risk neuroblastoma, GD2-CART01 (Bambino Gesù phase 1/2), Crystal L. Mackall, Neuroblastoma (paediatric).
- InstitutionSt. Jude Children's Research Hospital
Shares Julie R. Park, Osteosarcoma, Neuroblastoma (paediatric), Rare and paediatric cancers without markets.
- TrialNaxitamab Study 201
Shares Naxitamab, Neuroblastoma (paediatric), Rare and paediatric cancers without markets.
- InstitutionThe Hospital for Sick Children (SickKids)
Shares Texas Children's Cancer and Hematology Center, Neuroblastoma (paediatric), Rare and paediatric cancers without markets, Glioma & glioblastoma.
- TrialSIOPEN HR-NBL1
Shares Dinutuximab (ch14.18) / dinutuximab beta, Neuroblastoma (paediatric), Rare and paediatric cancers without markets.
- IdeaAdvance market commitments for paediatric and rare cancer drugs
Shares Neuroblastoma (paediatric), Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST), Glioma & glioblastoma.
- TermFNCLCC grade (soft-tissue sarcoma)
Shares Osteosarcoma, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST).