Table 1.
Current and promising immunotherapeutic strategies involving tumor-associated gangliosides.
| Ganglioside | Type of treatment | Description | Type of acquired immunity | Phase of clinical research | Type of human tumor | Reference |
|---|---|---|---|---|---|---|
| N-glycolyl-GM3 | Anti-idiotype Ab (racotumomab) | Murine gamma-type anti-idiotype monoclonal antibody that specifically induces an antibody response to Neu5Gc-containing gangliosides, sulfatides, and other antigens expressed in tumors | Active | Phase III trial | Non-small-cell lung cancer | (102, 113, 114) |
| GD2 | A chimeric Hu-murine antibody | Anti-GD2 Ab Ch14.18 + GM-CSF + IL-2 + isotretinoin | Passive | Phase I trial | High-risk neuroblastoma | (115) |
| Anti-GD2 Ab (hu14.18K322A). Humanized anti-GD2 Ab with a single point mutation (K322A) that reduces complement-dependent lysis | Phase I trial | Refractory or recurrent neuroblastoma | (116) | |||
| Immunocitokine chimeric hu14.18 Ab-IL2 | Hu14.18-IL2 fusion protein consists of interleukin-2 molecularly linked to a humanized monoclonal antibody that recognizes the GD2 | Phase II trial | Relapsed/refractory neuroblastoma | (117) | ||
| metastatic melanoma | (118, 119) | |||||
| CAR | Natural killer-92 cells stably express a GD2-specific CAR, which carries a cell-binding domain derived from antibody ch14.18 | Preclinical | – | (120) | ||
| Cell line: Hu neuroblastoma | ||||||
| Anti-idiotype Ab (gangliomab) | Immunization of Balb/c mice with 14G2a (murine monoclonal antibody to GD2), and splenocytes were harvested to generate hybridoma cells. Clones were screened for mouse antibody binding to hu14.18 | Active | Preclinical | – | (121) | |
| Cell line: Hu neuroblastoma | ||||||
| Inhibitor | Triptolide, a small molecule inhibitor, inhibits ST8-SiaI expression, GD2 biosynthesis, and cancer stem cells-associated properties | – | Preclinical | – | (122–124) | |
| Cell line: Hu breast cancer/human tissue | ||||||
| GD3 | Targeted delivery of cytotoxic agents | Secondary antibody coupled to Zap bounded to the mouse antibody to GD3 R24 | – | Preclinical | – | (109) |
| Cell line: Hu and mouse melanoma | ||||||
| Targeted delivery of cytotoxic agents | Secondary antibody coupled to Zap bounded to NG2 and a GD3A9-O-acetyl GD3 antibodies | – | (110) | |||
| Cell line: Hu glioblastoma multiforme | ||||||
| CAR | Anti-GD3 tandem chimeric sFv-CD28/T-cell receptor zeta designer T cells. Second generation | Passive | (90) | |||
| Cell line: human melanoma. Model animal: BALB/c nude mice | ||||||
| GM2 | Synthetic carbohydrate-based vaccines | Unimolecular pentavalent construct KLH conjugate (UPC-KLH, 2). Five prostate and breast cancer-associated carbohydrate antigens, globo-H, GM2, STn, TF, and Tn conjugated to the carrier protein KLH | Active | Preclinical | – | (125) |
| Model animal: mice (C57BL/6J) |
Ab, antibody; NG2, neuron-glia 2 (a transmembrane chondroitin sulfate proteoglycan); CAR, chimeric antigen receptors; Hu, human; KLH, keyhole limpet hemocyanin; Tn antigen, Thomsen-nouvelle antigen (GalNAcα1-O-Ser/Thr); STn, sialyl-Tn; TF, Thomsen–Friedenreich antigen; Zap, saporin.