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Syntheses and Functional Studies of Self‐Adjuvanting Anti‐HER2 Cancer Vaccines
Author(s) -
Feng Qi,
Manabe Yoshiyuki,
Kabayama Kazuya,
Aiga Taku,
Miyamoto Asuka,
Ohshima Shino,
Kametani Yoshie,
Fukase Koichi
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201901002
Subject(s) - epitope , lipopeptide , conjugate , tandem repeat , immune system , antibody , peptide , titer , antibody titer , in vivo , chemistry , recombinant dna , microbiology and biotechnology , biology , cancer research , immunology , biochemistry , mathematical analysis , genetics , mathematics , genome , bacteria , gene
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 Pam 3 CSK 4 via iterative condensation reaction. The in vivo results showed the Pam 3 CSK 4 ‐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 Pam 3 CSK 4 ‐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 Pam 3 CSK 4 , which provided useful evidence for developing further anti‐HER2 cancer vaccines.