PMID- 32707803
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201028
IS  - 2076-393X (Print)
IS  - 2076-393X (Electronic)
IS  - 2076-393X (Linking)
VI  - 8
IP  - 3
DP  - 2020 Jul 22
TI  - Enhanced Immunogenicity of Engineered HER2 Antigens Potentiates Antitumor Immune 
      Responses.
LID - 10.3390/vaccines8030403 [doi]
LID - 403
AB  - 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.
FAU - Jeon, Insu
AU  - Jeon I
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Lee, Jeong-Mi
AU  - Lee JM
AD  - Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College 
      of Pharmacy Seoul National University, Seoul 08826, Korea.
FAU - Shin, Kwang-Soo
AU  - Shin KS
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Kang, Taeseung
AU  - Kang T
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Park, Myung Hwan
AU  - Park MH
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Seo, Hyungseok
AU  - Seo H
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Song, Boyeong
AU  - Song B
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Koh, Choong-Hyun
AU  - Koh CH
AD  - Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College 
      of Pharmacy Seoul National University, Seoul 08826, Korea.
FAU - Choi, Jeongwon
AU  - Choi J
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Shin, Young Kee
AU  - Shin YK
AUID- ORCID: 0000-0003-0896-718X
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
FAU - Kim, Byung-Seok
AU  - Kim BS
AUID- ORCID: 0000-0002-8388-4942
AD  - Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon 
      National University, Incheon 22012, Korea.
FAU - Kang, Chang-Yuil
AU  - Kang CY
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
AD  - Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College 
      of Pharmacy Seoul National University, Seoul 08826, Korea.
AD  - Cellid, Inc., Seoul 08826, Korea.
LA  - eng
GR  - NRF-2018R1A2A1A05077627/Basic Science Research Program/
GR  - NRF-2016M3A9B5941426/Bio & Medical Technology Development Program/
PT  - Journal Article
DEP - 20200722
PL  - Switzerland
TA  - Vaccines (Basel)
JT  - Vaccines
JID - 101629355
PMC - PMC7563373
OTO - NOTNLM
OT  - HER2
OT  - cancer vaccine
OT  - p95HER2
COIS- C.Y.K. is employed as the chief executive officer of Cellid, Inc. The remaining 
      authors declare no competing financial interests.
EDAT- 2020/07/28 06:00
MHDA- 2020/07/28 06:01
PMCR- 2020/07/22
CRDT- 2020/07/26 06:00
PHST- 2020/06/24 00:00 [received]
PHST- 2020/07/14 00:00 [revised]
PHST- 2020/07/20 00:00 [accepted]
PHST- 2020/07/26 06:00 [entrez]
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2020/07/28 06:01 [medline]
PHST- 2020/07/22 00:00 [pmc-release]
AID - vaccines8030403 [pii]
AID - vaccines-08-00403 [pii]
AID - 10.3390/vaccines8030403 [doi]
PST - epublish
SO  - Vaccines (Basel). 2020 Jul 22;8(3):403. doi: 10.3390/vaccines8030403.