PMID- 38203458
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 1
DP  - 2023 Dec 24
TI  - Preclinical and Clinical Observations Implying Combination Therapy to Enhance the 
      Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent 
      Immune Evasion.
LID - 10.3390/ijms25010287 [doi]
LID - 287
AB  - Her-2/neu-targeting therapy by passive application with trastuzumab is associated 
      with acquired resistance and subsequent metastasis development, which is 
      attributed to the upregulation of tumoral PD-L1 expression and the downregulation 
      of Her-2/neu. We aimed to investigate this association, following active 
      immunization with our recently constructed B-cell peptide-based Her-2/neu 
      vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), 
      fluorescence in situ hybridization (FISH), and combined positive score (CPS) were 
      applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor 
      model for Her-2/neu lung metastases and tumor biopsies from a gastric cancer 
      patient with disease progression. A significant and concomitant reduction in 
      Her-2/neu and the upregulation of PD-L1 expression was observed in vaccinated 
      mice after 45 days, but not after 30 days, of metastases development. A 
      significant increase in tumor-infiltrating B lymphocytes was observed at both 
      time points. The downregulation of Her-2/neu and the upregulation of PD-L1 were 
      observed in a patient's primary tumor at the disease progression time point but 
      not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 
      0% to 5%). Our results further underline the need for combination therapy by 
      targeting PD-L1 to prevent metastasis formation and immune evasion of 
      Her-2/neu-positive and PD-L1-negative tumor cells.
FAU - Tobias, Joshua
AU  - Tobias J
AUID- ORCID: 0000-0002-0961-5306
AD  - Institute of Specific Prophylaxis and Tropical Medicine, Center for 
      Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 
      Vienna, Austria.
FAU - Hogler, Sandra
AU  - Hogler S
AUID- ORCID: 0000-0002-6899-5273
AD  - Institute of Pathology, Unit of Laboratory Animal Pathology, University of 
      Veterinary Medicine Vienna, 1210 Vienna, Austria.
FAU - Raigel, Martin
AU  - Raigel M
AD  - Institute of Pathology, Unit of Laboratory Animal Pathology, University of 
      Veterinary Medicine Vienna, 1210 Vienna, Austria.
FAU - Lin, Diego Shih-Chieh
AU  - Lin DS
AD  - Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
FAU - Chao, Yee
AU  - Chao Y
AUID- ORCID: 0000-0001-5578-340X
AD  - Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
FAU - Kenner, Lukas
AU  - Kenner L
AUID- ORCID: 0000-0003-2184-1338
AD  - Department of Experimental Pathology, Medical University of Vienna, 1090 Vienna, 
      Austria.
FAU - Garner-Spitzer, Erika
AU  - Garner-Spitzer E
AUID- ORCID: 0000-0002-5283-0458
AD  - Institute of Specific Prophylaxis and Tropical Medicine, Center for 
      Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 
      Vienna, Austria.
FAU - Yavrom, Sharon
AU  - Yavrom S
AD  - Imugene Limited, Sydney, NSW 2000, Australia.
FAU - Ede, Nicholas J
AU  - Ede NJ
AUID- ORCID: 0000-0003-4741-5855
AD  - Imugene Limited, Sydney, NSW 2000, Australia.
FAU - Zielinski, Christoph C
AU  - Zielinski CC
AD  - Central European Cancer Center, Wiener Privatklinik, and Central European 
      Cooperative Oncology Group (CECOG), 1090 Vienna, Austria.
FAU - Kundi, Michael
AU  - Kundi M
AUID- ORCID: 0000-0002-2707-3213
AD  - Department of Environmental Health, Center for Public Health, Medical University 
      of Vienna, 1090 Vienna, Austria.
FAU - Wiedermann, Ursula
AU  - Wiedermann U
AD  - Institute of Specific Prophylaxis and Tropical Medicine, Center for 
      Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 
      Vienna, Austria.
LA  - eng
PT  - Journal Article
DEP - 20231224
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *B7-H1 Antigen
MH  - Immune Evasion
MH  - In Situ Hybridization, Fluorescence
MH  - Oncogenes
MH  - *Cancer Vaccines/therapeutic use
MH  - Disease Progression
PMC - PMC10778754
OTO - NOTNLM
OT  - Her-2/neu
OT  - PD-L1
OT  - combination therapy
OT  - expression
OT  - immune evasion
OT  - preclinical and clinical settings
COIS- J.T., S.H, M.R., D.S.-C.L.,Y.C., L.K., E.G-S., M.K.: declare no potential 
      conflicts of interest. S.Y. and N.J.E.: Imugene Limited (Employment). C.C.Z.: 
      Consultation (Athenex, MSD, Imugene Limited (until September 2018), AstraZeneca, 
      Servier, Eli Lilly); Institutional (Eli Lilly, BMS, MSD, Pfizer, AstraZeneca, 
      Merck Amgen, Servier, Takeda, Daiichi Roche, Boehringer, Celgene, Halozyme). 
      U.W.: Imugene Limited (Consultation, until September 2018); GSK, Pfizer, Themis 
      (Funding to the Institute).
EDAT- 2024/01/11 07:43
MHDA- 2024/01/12 06:42
PMCR- 2023/12/24
CRDT- 2024/01/11 01:18
PHST- 2023/11/20 00:00 [received]
PHST- 2023/12/19 00:00 [revised]
PHST- 2023/12/22 00:00 [accepted]
PHST- 2024/01/12 06:42 [medline]
PHST- 2024/01/11 07:43 [pubmed]
PHST- 2024/01/11 01:18 [entrez]
PHST- 2023/12/24 00:00 [pmc-release]
AID - ijms25010287 [pii]
AID - ijms-25-00287 [pii]
AID - 10.3390/ijms25010287 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Dec 24;25(1):287. doi: 10.3390/ijms25010287.