Perez Sonia A, Peoples George E, Papamichail Michael, Baxevanis Constantin N
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
Methods Mol Biol. 2014;1139:321-36. doi: 10.1007/978-1-4939-0345-0_26.
A novel method for amplifying the activity of major histocompatibility complex (MHC) class II helper epitopes entails linking a 4-amino-acid moiety (LRMK) from the invariant chain (Ii) of MHC (referred to as Ii-Key) to the N-terminal end of the epitope peptide either directly or using a simple polymethylene spacer (-ava-). Ii-Key catalyzes binding of the linked epitope to the MHC class II molecule, thereby enhancing the overall potency of presentation. HER-2(776-790) (or AE36), which is derived from the intracellular domain of HER-2/neu, has been intensively used as an Ii-key/HER-2(776-790) (or AE37) fusion (hybrid) vaccine in clinical trials. This chapter describes procedures for the synthesis, reconstitution, sterility testing, and storage of both AE36 and AE37 for their use in clinical trials. Also provided is a detailed information about their in vivo administration and analysis of in-depth protocols for monitoring of immune activation upon vaccination with AE37.
一种增强主要组织相容性复合体（MHC）II类辅助表位活性的新方法，是将来自MHC恒定链（Ii）的一个4氨基酸部分（LRMK）（称为Ii-Key）直接或使用简单的聚亚甲基间隔基（-ava-）连接到表位肽的N末端。Ii-Key催化连接的表位与MHC II类分子的结合，从而增强呈递的整体效力。HER-2(776-790)（或AE36），它源自HER-2/neu的细胞内结构域，在临床试验中已被广泛用作Ii-key/HER-2(776-790)（或AE37）融合（杂交）疫苗。本章描述了AE36和AE37在临床试验中的合成、重构、无菌测试和储存程序。还提供了关于它们体内给药以及用于监测AE37疫苗接种后免疫激活的深入方案分析的详细信息。
