Enhanced Immunogenicity of Engineered HER2 Antigens Potentiates Antitumor Immune Responses release_elv546gyf5gxhpodkyfugppwfy

by Insu Jeon, Jeong-Mi Lee, Kwang-Soo Shin, Taeseung Kang, Myung Hwan Park, Hyungseok Seo, Boyeong Song, Choong-Hyun Koh, Jeongwon Choi, Young Kee Shin, BYUNG-SEOK KIM, Chang-Yuil Kang

Published in Vaccines by MDPI AG.

2020   Volume 8, Issue 3, p403


For cancer vaccines, the selection of optimal tumor-associated antigens (TAAs) that can maximize the immunogenicity of the vaccine without causing unwanted adverse effects is challenging. In this study, we developed two engineered Human epidermal growth factor receptor 2 (HER2) antigens, K965 and K1117, and compared their immunogenicity to a previously reported truncated HER2 antigen, K684, within a B cell and monocyte-based vaccine (BVAC). We found that BVAC-K965 and BVAC-K1117 induced comparable antigen-specific antibody responses and antigen-specific T cell responses to BVAC-K684. Interestingly, BVAC-K1117 induced more potent antitumor activity than the other vaccines in murine CT26-HER2 tumor models. In addition, BVAC-K1117 showed enhanced antitumor effects against truncated p95HER2-expressing CT26 tumors compared to BVAC-K965 and BVAC-K684 based on the survival analysis by inducing T cell responses against intracellular domain (ICD) epitopes. The increased ICD epitope-specific T cell responses induced by BVAC-K1117 compared to BVAC-K965 and BVAC-K684 were recapitulated in human leukocyte antigen (HLA)-untyped human PBMCs and HLA-A*0201 PBMCs. Furthermore, we also observed synergistic antitumor effects between BVAC-K1117 and anti-PD-L1 antibody treatment against CT26-HER2 tumors. Collectively, our findings demonstrate that inclusion of a sufficient number of ICD epitopes of HER2 in cellular vaccines can improve the antitumor activity of the vaccine and provide a way to optimize the efficacy of anticancer cellular vaccines targeting HER2.
In application/xml+jats format

Archived Files and Locations

application/pdf  2.6 MB
res.mdpi.com (publisher)
web.archive.org (webarchive)
Read Archived PDF
Type  article-journal
Stage   published
Date   2020-07-22
Language   en ?
Container Metadata
Open Access Publication
In Keepers Registery
ISSN-L:  2076-393X
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
Catalog Record
Revision: a7d10d99-fc9c-4fb5-a03a-0faac289da80