Syntheses and Functional Studies of Self-Adjuvanting Anti-HER2 Cancer Vaccines

Abstract

The 9-mer peptide MFCH401 (N: 165-173: DTILWKDIF), which is located in the extracellular domain of HER2, has been predicted to be a novel epitope. Self-adjuvanting anti-HER2 vaccine constructs were designed and synthesized via covalently attaching MFCH401 or its linear tandem repeats (2×MFCH401, 3×MFCH401) to a lipopeptide Pam₃ CSK₄ via iterative condensation reaction. The in vivo results showed the Pam₃ CSK₄ -MFCH401 vaccine construct can induce higher antibody titers of IgG and IgM than those of other conjugates, and the analysis of changes in plasma cytokines level indicate the activation of Th1 cells and NK cells. In addition, the Pam₃ CSK₄ -MFCH401 vaccine conjugate induced a specific immune response to HER2-overexpressing human BT474 cells. Our data clearly indicated that MFCH401 is a promising epitope; moreover, its linear tandem repeats were unsuitable for anticancer vaccine design when conjugating with Pam₃ CSK₄ , which provided useful evidence for developing further anti-HER2 cancer vaccines.

Keywords: CH401; HER2; Pam3CSK4; cancer vaccine; self-adjuvanting.