Systematic amino acid substitutions improved efficiency of GD₂-peptide mimotope vaccination against neuroblastoma

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• 作者：Matthias Bleeke ; Stefan Fest ; Nicole Huebener ; Christiane L ; graf ; Burkhart Schraven ; Gerhard Gaedicke ; Rudolf Volkmer ; Holger N. Lode
• 关键词：Immunotherapy ; Neuroblastoma ; Ganglioside ; Mimotope ; SPOT
• 刊名：European Journal of Cancer
• 出版年：2009
• 出版时间：November 2009
• 年：2009
• 卷：45
• 期：16
• 页码：2915-2921
• 全文大小：374 K

文摘

The likelihood of identifying peptides of sufficient quality for the development of effective cancer vaccines by screening of phage display libraries is low. Here, we introduce the sequential application of systematic amino acid substitution by SPOT synthesis. After the substitution of two amino acids within the sequence of a phage display-derived mimotope of disialoganglioside GD₂ (mimotope MA), the novel mimotope C3 showed improved GD₂ mimicry in vitro. Peptide vaccination with the C3 mimotope induced an 18-fold increased anti-GD₂ serum response associated with reduction of primary tumour growth and spontaneous metastasis in contrast to MA mimotope controls in a syngeneic neuroblastoma model. In summary, SPOT provides an ideal optimisation tool for the development of phage display-derived cancer vaccines.