title: Invariant chain-peptide fusion vaccine using HER-2/neu.
abstract: 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.
authors.affiliation: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Perez
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
authors.forename: Michael
authors.initials: M
authors.lastname: Papamichail
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Baxevanis
mesh_terms: D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; C045084:invariant chain