HER2 vaccine, AE37 Sample Clauses

HER2 vaccine, AE37. The HER2/neu proto-oncogene is a tumor associated antigen that has been investigated in many types of cancers including breast, prostate, and ovarian. HER2/neu codes for a 185kD trans-membrane protein in the epidermal growth factor receptor family which is found to be over- expressed in 20-30% of breast cancers and has also been correlated with more aggressive tumor behavior (Slamon 1989). It has been shown to be expressed in an additional 50% of breast cancers at low to intermediate levels. AE37 is a fifteen amino-acid peptide from the HER2 protein to which the four amino-acid sequence LRMK has been added, it is produced by a solid-phase peptide synthesis. The peptide sequence is AC-LRMK-GVGSPYVSRLLGICL-NH2. Studies have demonstrated that the AE37 peptide stimulates a robust helper T-cell response leading to effective cytotoxic T lymphocyte (CTL) activity against tumors expressing even low levels of HER2 regardless of HLA status. AE37 is a hybrid Ii-Key/HER2 peptide. Ii-Key hybrids have been shown to display >250 times potency in terms of T-cell stimulation in vitro compared to the unmodified naturally-occurring peptide. AE37 has been shown to be recognized both by CD4+ T helper cells as well as CD8+ CTLs (HER2 Hybrid Peptide AE37 IB). Antigen Express has developed a novel method for dramatically increasing antigen-specific stimulation of T helper cells. This involves the addition of a small portion of the major histocompatibility complex (MHC) class II-associated Ii protein (termed Ii-Key) to class II epitopes (Xxx 2000). The Ii-Key segment of the Ii protein was found to bind to an allosteric site on MHC class II molecules, thereby facilitating the direct charging of a vaccine peptide into the antigenic peptide-binding site of MHC class II molecules (Sotiriadou 2007). The resulting Ii- Key/antigenic epitope hybrid displays up to 250 times greater potency in vitro compared to the unmodified class II epitope (Sotiriadou 2007). Studies have shown that Ii-Key hybrid peptides derived from a variety of disease-related antigens more potently activate CD4+ T helper cells in vivo as well as in vitro when compared to epitope only peptides. The consequence of this increased yet specific T helper cell stimulation is more robust CTL activation and the production of immunological memory.
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