Gangliosides

Living reference work entry
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Abstract

Gangliosides are acidic glycosphingolipids that are expressed on the cell surface where they may play a role in the metastatic process and have proven to be uniquely potent targets for antibody-mediated immune attack using cancer vaccines or monoclonal antibodies. Five gangliosides are important targets for cancer therapy: GM2, GD2, and GD3 expressed primarily on tumors of neuroectodermal origin such as neuroblastomas, sarcomas, and melanomas; fucosyl GM1 expressed on small-cell lung cancers; and sialyl Lewisa (Lea), also known as CA19.9, expressed on cancers of the colon, pancreas, and breast. Vaccines and especially monoclonal antibodies targeting GD2, GD3, and sLea are able to prevent tumor establishment or slow tumor growth in preclinical models, but regression of visible or palpable tumors has proven more difficult. Recently, this has proven possible with radioimmune or antibody drug conjugates targeting sLea. These types of monoclonal antibody conjugates may represent the future of ganglioside-targeted therapy. Randomized clinical trials with vaccines targeting GM2, GD2, and GD3 gangliosides have been negative to date. However, randomized clinical trials with monoclonal antibodies targeting GD2 (UnituxinTM) in neuroblastoma patients have been positive, and UnituxinTM is now FDA approved for treatment of high-risk neuroblastoma patients. Radioimmune or antibody drug conjugates targeting gangliosides have not yet been tested in the clinic.

Keywords

Gangliosides Glycosphingolipids Cancer Vaccines Monoclonal Antibodies (mAbs) GM2 GD2 GD3 Fucosyl GM1 sLea CA19.9 Antibody-drug Conjugates 
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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Melanoma and Sarcoma ServiceMemorial Sloan-Kettering Cancer Center (retired)New YorkUSA
  2. 2.MabVax Therapeutics IncSan DiegoUSA
  3. 3.Memorial Sloan-Kettering Cancer CenterNew YorkUSA

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