GD2-GANGLIOSIDE

• CAS: 65988-71-8
• Catalog Number: ACM65988718
• Category: Main Products
• Molecular Weight: 1591.86
• Molecular Formula: C74H134N4O32
• Appearance: Film (dried in situ)

Case Study

GD2-Ganglioside as Target for Anti-GD2 Immunotherapy in Neuroblastoma

Doronin, Igor I., et al. BMC cancer 14.1 (2014): 295.

Ganglioside GD2 is a tumor-associated glycosphingolipid expressed at high levels on the plasma membrane of malignant cells, particularly those of neuroectodermal origin. While anti-GD2 monoclonal antibodies (mAbs) are known to act through complement-dependent cytotoxicity and antibody-mediated cellular cytotoxicity, their potential for direct cell death induction had not been thoroughly investigated. Doronin, I., et al. examined the functional role of GD2 as a receptor capable of actively transducing death signals in tumor cells.
Experimental Protocol: GD2 expression on various tumor cell lines (EL-4, L1210, Jurkat, IMR-32, Neuro-2A, mS, A375) was analyzed by flow cytometry using anti-GD2 antibodies. The amount of GD2 in total ganglioside fractions was quantified by high-performance thin-layer chromatography (HPTLC) with densitometric analysis. Cell viability was assessed by MTT assay after treatment with anti-GD2 mAbs. Cross-reactivity with other gangliosides was evaluated by ELISA and flow cytometry. GD2 expression was inhibited using the glucosylceramide synthase inhibitor PDMP and siRNA targeting GM2/GD2 and GD3 synthases. Cell death mechanisms were characterized by monitoring mitochondrial membrane potential, apoptotic volume decrease, and membrane permeability.
Performance Evaluation: Anti-GD2 mAbs effectively induced cell death exclusively in GD2-positive tumor cells, with no effect on GD2-negative cells. The cytotoxic effect was mediated specifically by antibody binding to GD2, not through cross-reactivity with other surface molecules. GD2 expression level correlated directly with susceptibility to the cytotoxic effect. Cell death proceeded through mitochondrial membrane potential alteration and increased membrane permeability. Inhibition of GD2 synthesis by PDMP or siRNA reduced the cytotoxic response. These findings establish GD2 as a functional receptor that actively transduces death signals, providing a mechanistic basis for the direct tumoricidal activity of anti-GD2 antibodies.

GD2-Ganglioside for CAR-T Cell Targeting in Solid Tumor Therapy

Battula, Venkata Lokesh, et al. The Journal of clinical investigation 122.6 (2012): 2066-2078.

Battula, V., et al. discovered that ganglioside GD2, a b-series glycosphingolipid, identifies a small fraction of cells in human breast cancer cell lines and patient samples that possess CSC properties. The study demonstrated that GD2-positive cells were capable of forming mammospheres and initiating tumors with as few as 10 cells in immunocompromised mice. Importantly, most GD2-positive cells also exhibited the CD44hi/CD24lo phenotype, the previously established CSC-associated cell surface marker profile, providing convergent validation of their stem-like identity.
Experimental Protocol: GD2 expression was analyzed in human breast cancer cell lines and patient samples by flow cytometry. GD2-positive and GD2-negative populations were isolated by fluorescence-activated cell sorting (FACS). Mammosphere formation assays assessed in vitro self-renewal capacity. In vivo tumor initiation was evaluated by limiting dilution transplantation into NOD/SCID mice. Gene expression analysis identified differentially expressed genes between populations. GD3 synthase (GD3S) expression was knocked down using shRNA and pharmacological inhibition. Epithelial-mesenchymal transition (EMT) was induced in HMLER cells by ectopic expression of Snail/Twist or by TGF-beta treatment.
Performance Evaluation: GD2-positive cells demonstrated significantly enhanced mammosphere formation and tumor initiation capacity compared to GD2-negative cells, with tumors forming from as few as 10 GD2-positive cells. GD3S was identified as highly expressed in both GD2-positive and CD44hi/CD24lo cells. Knockdown of GD3S expression by shRNA or pharmacological inhibition reduced the CSC population and CSC-associated properties in vitro and completely abrogated tumor formation in vivo. Induction of EMT dramatically increased both GD2 and GD3S expression, suggesting EMT plays a role in the origin of GD2-positive breast CSCs. GD2 was thus established as a novel CSC-specific marker and GD3S as a potential therapeutic target.

GD2-Ganglioside as Diagnostic Marker and Therapeutic Target in Pediatric Cancers

Roth, Michael, et al. Cancer 120.4 (2014): 548-554.

Osteosarcoma is the most common primary bone tumor in childhoods. Ganglioside GD2 has proven to be an effective target for antibody-mediated immunotherapy in neuroblastoma. Roth, M., et al. systematically examined the expression pattern of GD2 in osteosarcoma tumor samples obtained at initial biopsy, definitive surgery, and disease recurrence. The study also quantified GD2 expression levels across a panel of osteosarcoma cell lines and compared them with a neuroblastoma cell line, which is the established clinical target for anti-GD2 therapy.
Experimental Protocol: Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded osteosarcoma tissue microarray samples. A total of 44 samples were evaluated: 8 from initial biopsy, 28 from definitive surgery, and 8 from disease recurrence. Staining intensity and location were scored by two independent observers blinded to sample timing. Cell-based enzyme-linked immunosorbent assay (ELISA) was performed on 24 short-term osteosarcoma primary cell cultures to quantify GD2 expression levels. The neuroblastoma cell line BE(2)-C served as a positive control. Control melanoma tissue was used for IHC staining comparison.
Performance Evaluation: GD2 was expressed on all 44 osteosarcoma samples evaluated by IHC, demonstrating universal expression across the disease spectrum. Importantly, osteosarcoma tissue obtained at the time of disease recurrence demonstrated significantly higher staining intensity compared with samples from initial biopsy and definitive surgery (P=0.016), suggesting that GD2 expression may increase with disease progression. The majority of osteosarcoma cell lines expressed GD2 at higher levels than the neuroblastoma cell line BE(2)-C, which is the established benchmark for anti-GD2 immunotherapy. These findings provide strong rationale for clinical trials evaluating anti-GD2 antibody-mediated therapy in patients with osteosarcoma, particularly in the recurrent setting where GD2 expression is most pronounced.

Custom Q&A

What is the molecular formula of GD2-Ganglioside?

The molecular formula of GD2-Ganglioside is C74H134N4O32.

What is the molecular weight of GD2-Ganglioside?

The molecular weight of GD2-Ganglioside is 1591.9 g/mol.

When was GD2-Ganglioside created?

GD2-Ganglioside was created on December 4, 2007.

When was GD2-Ganglioside last modified?

GD2-Ganglioside was last modified on October 21, 2023.

What is the IUPAC name of GD2-Ganglioside?

The IUPAC name of GD2-Ganglioside is 2-[3-[6-[5-[3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[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.

What is the InChI of GD2-Ganglioside?

The InChI of GD2-Ganglioside is 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+.

What is the InChIKey of GD2-Ganglioside?

The InChIKey of GD2-Ganglioside is FFILOTSTFMXQJC-NHQGMKOOSA-N.

What is the Canonical SMILES of GD2-Ganglioside?

The Canonical SMILES of GD2-Ganglioside is CCCCCCCCCCCCCCCCC(=O)NC(COC1C(C(C(C(O1)CO)OC2C(C(C(C(O2)CO)OC3C(C(C(C(O3)CO)O)O)NC(=O)C)OC4(CC(C(C(O4)C(C(COC5(CC(C(C(O5)C(C(CO)O)O)N)O)C(=O)O)O)O)N)O)C(=O)O)O)O)O)C(C=CCCCCCCCCCCCC)O.

What is the XLogP3-AA value of GD2-Ganglioside?

The XLogP3-AA value of GD2-Ganglioside is -1.9.

How many hydrogen bond donor counts does GD2-Ganglioside have?

GD2-Ganglioside has 22 hydrogen bond donor counts.