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Gangliosides

N-glycolylneuraminic acid (Neu5Gc, NGNA, NeuGc, N-glycolil, Ngc) gangliosides are practically undetectable in healthy human tissues and fluids. This is because human cells lack the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) due to a genetic mutation that occurred more than 2.5 million years ago [1]. Nonetheless, the N-glycolylneuraminic acid-GM3 gangliosises (NGcGM3) are highly expressed in several human cancers, including lung, breast, melanoma, as well as neuroectodermal pediatric tumors.

Vaxira® is a therapeutic vaccine for the treatment of non-small cell lung cancer (NSCLC). It is composed of racotumomab> and aluminum hydroxide adjuvant.

Racotumomab (1E10) antibody binds to the idiotype of the antibody P3 which is quite specific for the recognition of N-glycolyl ceramides of mono-sialyl lactose..

Thus, racotumomab is an anti-idiotypic mouse monoclonal antibody that mimics the N-glycolylneuraminic acid-GM3 gangliosides, thus triggering an immune response against the tumor antigen NGcGM3.

References:

[1] Chou, H. H., Takematsu, H., Diaz, S., Iber, J., Nickerson, E., Wright, K. L., et al. (1998). A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence. Proc. Natl. Acad. Sci. U.S.A. 95, 11751-11756.PMC21712