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Pathogenesis of the neurotoxicity caused by anti-GD2 antibody therapy
1Department of Biochemistry, Faculty of Medicine, Tokyo Medical and Dental University, Japan. yuki@dokkyomed.ac.jp
Abstract:
After treatment of melanomas with anti-GD2 monoclonal antibody (MAb) (14G2a), some patients develop sensorimotor demyelinating polyneuropathy with and without the syndrome of inappropriate antidiuretic hormone (SIADH). To clarify what causes the neurotoxicity of anti-GD2 MAb, we investigated the immunohistochemical localization of GD2 in the human nervous system. Anti-GD2 MAb (14G2a) reacted with the myelin sheaths in the peripheral nerves as well as with the pituicyte cytoplasm in the posterior lobe of the pituitary gland. We assume that the binding of anti-GD2 MAb to peripheral nerve myelin and the pituicytes in the posterior pituitary causes sensorimotor demyelinating neuropathy and SIADH.
Insights
Anti-GD2 monoclonal antibody (MAb) treatment for melanoma can cause neurotoxicity. This study found GD2 on peripheral nerve myelin and pituitary cells, explaining the observed sensorimotor neuropathy and SIADH.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Melanoma patients treated with anti-GD2 monoclonal antibody (MAb) can develop neurotoxic side effects.
- These side effects include sensorimotor demyelinating polyneuropathy and syndrome of inappropriate antidiuretic hormone (SIADH).
Purpose of the Study:
- To investigate the underlying cause of anti-GD2 MAb-induced neurotoxicity.
- To determine the localization of GD2 antigen within the human nervous system.
Main Methods:
- Immunohistochemical analysis of human nervous system tissues.
- Utilized anti-GD2 MAb (14G2a) for staining.
Main Results:
- GD2 antigen was localized to the myelin sheaths of peripheral nerves.
- GD2 was also found in the cytoplasm of pituicytes in the posterior pituitary gland.
Conclusions:
- The binding of anti-GD2 MAb to peripheral nerve myelin likely causes sensorimotor demyelinating polyneuropathy.
- Binding to posterior pituitary pituicytes is hypothesized to cause SIADH.