PMID- 24668647
OWN - NLM
STAT- MEDLINE
DCOM- 20150107
LR  - 20201222
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 20
IP  - 11
DP  - 2014 Jun 1
TI  - Chimeric rat/human HER2 efficiently circumvents HER2 tolerance in cancer 
      patients.
PG  - 2910-21
LID - 10.1158/1078-0432.CCR-13-2663 [doi]
AB  - PURPOSE: Despite the great success of HER2 vaccine strategies in animal models, 
      effective clinical results have not yet been obtained. We studied the feasibility 
      of using DNA coding for chimeric rat/human HER2 as a tool to break the 
      unresponsiveness of T cells from patients with HER2-overexpressing tumors 
      (HER2-CP). EXPERIMENTAL DESIGN: Dendritic cells (DCs) generated from patients 
      with HER2-overexpressing breast (n = 28) and pancreatic (n = 16) cancer were 
      transfected with DNA plasmids that express human HER2 or heterologous rat 
      sequences in separate plasmids or as chimeric constructs encoding rat/human HER2 
      fusion proteins and used to activate autologous T cells. Activation was evaluated 
      by IFN-gamma ELISPOT assay, perforin expression, and ability to halt HER2+ tumor 
      growth in vivo. RESULTS: Specific sustained proliferation and IFN-gamma production by 
      CD4 and CD8 T cells from HER2-CP was observed after stimulation with autologous 
      DCs transfected with chimeric rat/human HER2 plasmids. Instead, T cells from 
      healthy donors (n = 22) could be easily stimulated with autologous DCs 
      transfected with any human, rat, or chimeric rat/human HER2 plasmid. Chimeric 
      HER2-transfected DCs from HER2-CP were also able to induce a sustained T-cell 
      response that significantly hindered the in vivo growth of HER2(+) tumors. The 
      efficacy of chimeric plasmids in overcoming tumor-induced T-cell dysfunction 
      relies on their ability to circumvent suppressor effects exerted by regulatory T 
      cells (Treg) and/or interleukin (IL)-10 and TGF-beta1. CONCLUSIONS: These results 
      provide the proof of concept that chimeric rat/human HER2 plasmids can be used as 
      effective vaccines for any HER2-CP with the advantage of being not limited to 
      specific MHC. Clin Cancer Res; 20(11); 2910-21. (c)2014 AACR.
CI  - (c)2014 American Association for Cancer Research.
FAU - Occhipinti, Sergio
AU  - Occhipinti S
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Sponton, Laura
AU  - Sponton L
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Rolla, Simona
AU  - Rolla S
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Caorsi, Cristiana
AU  - Caorsi C
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Novarino, Anna
AU  - Novarino A
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Donadio, Michela
AU  - Donadio M
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Bustreo, Sara
AU  - Bustreo S
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Satolli, Maria Antonietta
AU  - Satolli MA
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Pecchioni, Carla
AU  - Pecchioni C
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Marchini, Cristina
AU  - Marchini C
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Amici, Augusto
AU  - Amici A
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Cavallo, Federica
AU  - Cavallo F
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Cappello, Paola
AU  - Cappello P
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Pierobon, Daniele
AU  - Pierobon D
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Novelli, Francesco
AU  - Novelli F
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy.
FAU - Giovarelli, Mirella
AU  - Giovarelli M
AD  - Authors' Affiliations: Departments of Molecular Biotechnology and Health 
      Sciences, University of Torino, Torino, Italy; Center for Experimental Research 
      and Medical Studies (CERMS), AO Citta della Salute e della Scienza di Torino, 
      Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta della 
      Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, ItalyAuthors' Affiliations: Departments of Molecular Biotechnology and 
      Health Sciences, University of Torino, Torino, Italy; Center for Experimental 
      Research and Medical Studies (CERMS), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Immunogenetic and Transplant Biology Service, AO Citta 
      della Salute e della Scienza Torino, Italy; Division of Oncology, Subalpine 
      OncoHematology Cancer Center (COES), AO Citta della Salute e della Scienza di 
      Torino, Torino, Italy; Department of Oncology, University of Turin, Orbassano, 
      Italy; Department of Medical Sciences, University of Torino, Torino, Italy, 
      Department of Molecular Cellular and Animal Biology, University of Camerino, 
      Camerino, Italy mirella.giovarelli@unito.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140325
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Cancer Vaccines)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Vaccines, DNA)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*immunology
MH  - Cancer Vaccines/*immunology/pharmacology
MH  - Dendritic Cells/immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immune Tolerance/immunology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Pancreatic Neoplasms/*immunology
MH  - Plasmids
MH  - Rats
MH  - Receptor, ErbB-2/*immunology
MH  - Recombinant Fusion Proteins/immunology/pharmacology
MH  - Transfection
MH  - Transplantation Chimera
MH  - Vaccines, DNA/*immunology/pharmacology
MH  - Xenograft Model Antitumor Assays
EDAT- 2014/03/29 06:00
MHDA- 2015/01/08 06:00
CRDT- 2014/03/27 06:00
PHST- 2014/03/27 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/01/08 06:00 [medline]
AID - 1078-0432.CCR-13-2663 [pii]
AID - 10.1158/1078-0432.CCR-13-2663 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2014 Jun 1;20(11):2910-21. doi: 10.1158/1078-0432.CCR-13-2663. 
      Epub 2014 Mar 25.