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Racotumomab〔World Health Organization(2008) (WHO Drug Information )〕 〔Pharmaceutical product authorized under special conditions by the Argentine Ministry of Health -Cert.N:57.031〕 (trade name Vaxira) is a therapeutic cancer vaccine for the treatment of solid tumors that is currently under clinical development by Recombio, an international public-private consortium with the participation of the Center of Molecular Immunology at Havana, Cuba (CIM) and researchers from Buenos Aires University and National University of Quilmes in Argentina.〔(Recombio )〕〔(Consorcio de investigación, desarrollo e innovación )〕 It induces the patient's immune system to generate a response against a cancer-specific molecular target with the purpose of blocking tumor growth, slowing disease progression and ultimately increasing patient survival. Racotumomab triggers an immune response against the tumor antigen N-glycolil (NGc) GM3 (NGcGM3), a type of ganglioside present on the cell surface of malignant cells from lung and breast, melanoma, as well as neuroectodermal pediatric tumors.〔Alfonso, M., Diaz, A., Hernandez, A.M., Perez, A., Rodriguez, E., Bitton, R., et al. (2002). An anti idiotype vaccine elicits a specific response to N-glycolylsialic acid residues of glycoconjugates in melanoma patients. J. Immunol. 168, 2523–2529.〕〔Scursoni, A.M., Galluzzo, L., Camarero, S., Lopez, J., Lubieniecki, F., Sampor,C., et al. (2011). Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer. Clin. Dev.Immunol. 2011:245181.〕〔van Cruijsen, H., Ruiz, M.G., van der Valk, P., de Gruijl, T.D., and Giaccone, G. (2009). Tissue microarray analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvesse ldensity in non-small cell lung cancer. BMC Cancer 9:180. doi:10.1186/1471- 2407-9-180.〕 Racotumomab has successfully completed a proof-of concept clinical trial in advanced non-small cell lung cancer (NSCLC) and is currently being tested in a large, multinational study for the same indication.〔http://www.clinicaltrials.gov/ct2/results?term=racotumomab&Search=Search〕 == Mechanism of action == Gangliosides are concentrated on the surface of mammalian cells and play an important role in cell growth and differentiation. NGc gangliosides, however, are practically undetectable in healthy human tissues and fluids due to a genetic deletion in the human gene that encodes the enzyme responsible for the synthesis of NGc, the CMP-N-acetyl hydroxylase.〔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.〕 Nonetheless, the NGcGM3 ganglioside is highly expressed in several human cancers, including lung, breast, melanocytes, colon and neuroectodermal pediatric tumors, making this neoantigen an attractive target for cancer therapy. Racotumomab is an anti-idiotypic mouse monoclonal antibody that mimics NGc gangliosides, thus triggering an immune response against the tumor antigen NGcGM3. Therefore, rather than being a passive antibody therapy, Racotumomab acts as a therapeutic vaccine. In melanoma, breast, and lung cancer patients, Racotumomab was able to elicit a specific immune response that recognized and directly killed tumor cells expressing the neoantigen by a mechanism of oncotic necrosis.〔Hernández, A.M., Rodríguez, N., González, J.E., Reyes, E., Rondón, T., Griñán, T., et al. (2011). Anti-NeuGcGM3 antibodies actively elicited by idiotypic vaccination in non-small cell lung cáncer patients induce tumor cell death by an oncosis-like mechanism. J. Immunol. 186, 3735–3744.〕 The specific expression of NGcGM3 in malignant cells reduces the potential risk of an immune cross-reactivity that could cause serious adverse effects. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Racotumomab」の詳細全文を読む スポンサード リンク
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