Issue 53, 2021

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines

Abstract

Breast cancer is the leading cause of cancer-related deaths among women worldwide. Human epidermal growth factor receptor 2 (HER2) overexpression is significantly associated with higher breast tumor proliferation rates. MFCH401, a 9-mer specific peptide fragment (DTILWKDIF) in the extracellular domain of the HER2 protein, is an attractive epitope for developing anti-HER2 cancer vaccines. However, the inherent low immunogenicity of MFCH401 limits its application. Herein, to induce a stronger and more durable immune response, a self-adjuvanting MFCH401-conjugated multiple-component anti-HER2 cancer vaccine was designed and synthesized by incorporating MFCH401 with lipopeptide Pam3CSK4 and a helper T cell epitope derived from tetanus toxoid P2 via an iterative condensation reaction. In vivo immunological evaluation demonstrated that the tricomponent anti-HER2 vaccine induced stronger humoral and cellular immune responses than the two-component conjugates. In addition, the induced antibodies effectively bound to HER2-overexpressing human BT474 cells. Our data clearly indicated that the MFCH401-based tricomponent anti-HER2 cancer vaccine could effectively enhance the immunogenicity of MFCH401. Structure–activity relationship analysis demonstrated that Pam3CSK4 confers better immunostimulatory activity than the helper T cell epitope P2 when conjugated with MFCH401.

Graphical abstract: Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
16 Aug 2021
Accepted
23 Sep 2021
First published
15 Oct 2021
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2021,11, 33814-33822

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines

Q. Feng, X. Yu, Y. Wang, S. Li and Y. Yang, RSC Adv., 2021, 11, 33814 DOI: 10.1039/D1RA06146A

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