The Many Lives of Antibodies to Gangliosides: Implications in Developing and Improvement of Immunotherapies

DANIOTTI J.L.

Vancouver

Conferencia; 16th IUBMB Conference; 2016

The International Union of Biochemistry and Molecular Biology (IUBMB)

Differentially expressed tumor-associated carbohydrates represent a general phenomenon observed in many types of cancer cells. Carbohydrates covalently attached to gangliosides, sialic acid-containing glycolipids, are not the exception. Neosynthesized gangliosides observed in oncogenic processes show antigen specificity and, therefore, they are attractive candidates for the design of cancer immunotherapies. In addition, antibodies to gangliosides have been associated with a wide range of neuropathy diseases and differential cell internalization of these antibodies is associated with different clinical outcome of the diseases. According to information obtained from our and other laboratories, antibodies to different gangliosides species do not share common features like membrane binding, cellular endocytosis and immune response. Rather, they behave in an epitope- and cell type-dependent manner. This information has important translational implications for the understanding of clinical characteristics of anti-glycolipid antibody-mediated neuropathies and for the development of innovative therapeutics targeting. In this sense, the disialo ganglioside GD3 has emerged as a novel and attractive class of cell surface molecule (glycolipid) for targeted delivery of drugs. Its accessibility, high expression in many tumor cells, and mainly its capacity to undergo endocytosis after binding with antibodies, has allowed us to develop an ablation cell strategy for selective intracellular delivery of cytotoxic agent to GD3-expressing cells, providing a rationale for future therapeutic intervention in cancer.