Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial.
Adult
Aged
Cancer Vaccines
/ administration & dosage
Cell Line, Tumor
Colorectal Neoplasms
/ drug therapy
Cytokines
/ metabolism
Disease-Free Survival
Esophageal Neoplasms
/ drug therapy
Female
HLA-A2 Antigen
/ metabolism
HLA-A24 Antigen
/ metabolism
HSP110 Heat-Shock Proteins
/ chemistry
Hep G2 Cells
Humans
Male
Middle Aged
Prognosis
T-Lymphocytes, Cytotoxic
/ immunology
Treatment Outcome
Vaccines, Subunit
/ administration & dosage
cancer vaccine
cytokine
cytotoxic T lymphocyte
heat shock protein 105
human leukocyte antigen
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
22
03
2019
revised:
02
08
2019
accepted:
05
08
2019
pubmed:
8
8
2019
medline:
12
10
2019
entrez:
8
8
2019
Statut:
ppublish
Résumé
Heat shock protein 105 (HSP105) is overexpressed in many cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We carried out a phase I clinical trial of HLA-A24- and HLA-A2-restricted HSP105 peptide vaccines in patients with CRC or EC. In this additional study of the trial, we examined the immunological efficacy of the novel vaccine. Thirty patients with advanced CRC or EC underwent HSP105 peptide vaccination. Immunological responses were evaluated by ex vivo and in vitro γ-interferon enzyme-linked immunospot assays and their correlation with patients' prognosis was analyzed. The HSP105 peptide vaccines induced peptide-specific CTLs in 15 of 30 patients. Among HLA-A24 patients (n = 15), 7 showed induction of CTLs only ex vivo, whereas among HLA-A2 patients (n = 15), 4 showed the induction ex vivo and 6 in vitro. Heat shock protein 105-specific CTL induction correlated with suppression of cancer progression and was revealed as a potential predictive biomarker for progression-free survival (P = .008; hazard ratio = 3.03; 95% confidence interval, 1.34-6.85) and overall survival (P = .025; hazard ratio = 2.72; 95% confidence interval, 1.13-6.52). Production of cytokines by HSP105 peptide-specific CTLs was observed at the injection sites (skin) and tumor tissues, suggesting that HSP105-specific CTLs not only accumulated at vaccination sites but also infiltrated tumors. Furthermore, we established 2 HSP105 peptide-specific CTL clones, which showed HSP105-specific cytokine secretion and cytotoxicity. Our results suggest that the HSP105 peptide vaccine could induce immunological effects in cancer patients and improve their prognosis.
Identifiants
pubmed: 31390678
doi: 10.1111/cas.14165
pmc: PMC6778658
doi:
Substances chimiques
Cancer Vaccines
0
Cytokines
0
HLA-A2 Antigen
0
HLA-A24 Antigen
0
HSP110 Heat-Shock Proteins
0
Vaccines, Subunit
0
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3049-3060Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP 16ck0106109 h0003
Organisme : National Cancer Center Research and Development Fund
ID : 25-7
Organisme : National Cancer Center Research and Development Fund
ID : 28-A-8
Informations de copyright
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Nat Med. 2012 Aug;18(8):1254-61
pubmed: 22842478
Science. 1996 Oct 4;274(5284):94-6
pubmed: 8810254
Mol Ther. 2011 Mar;19(3):620-6
pubmed: 21157437
N Engl J Med. 2015 Jun 25;372(26):2509-20
pubmed: 26028255
Biochem Biophys Res Commun. 2001 Mar 9;281(4):936-44
pubmed: 11237751
Clin Cancer Res. 2013 Apr 15;19(8):2224-31
pubmed: 23479678
Melanoma Res. 2008 Jun;18(3):166-71
pubmed: 18477890
Hum Vaccin Immunother. 2013 Jun;9(6):1234-6
pubmed: 23411443
Nat Med. 2003 Nov;9(11):1377-82
pubmed: 14528297
Lancet. 2014 Apr 26;383(9927):1490-1502
pubmed: 24225001
Lancet Oncol. 2017 Sep;18(9):1182-1191
pubmed: 28734759
J Immunol. 2006 Nov 1;177(9):6548-59
pubmed: 17056587
Int J Oncol. 2013 Oct;43(4):1019-26
pubmed: 23903757
Nat Immunol. 2002 Nov;3(11):999-1005
pubmed: 12407407
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Nat Rev Clin Oncol. 2014 Sep;11(9):509-24
pubmed: 25001465
J Clin Oncol. 2011 Mar 1;29(7):917-24
pubmed: 21282551
Int J Oncol. 2015 Jan;46(1):28-36
pubmed: 25354479
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Immunol Today. 1996 Apr;17(4):165-70
pubmed: 8871347
Tissue Antigens. 1997 Sep;50(3):277-82
pubmed: 9331950
Oncoimmunology. 2016 Jan 19;5(5):e1129483
pubmed: 27467945
Mol Med Today. 1999 Apr;5(4):178-86
pubmed: 10203751
Blood. 2009 Jul 16;114(3):535-46
pubmed: 19451549
Nat Rev Immunol. 2006 May;6(5):383-93
pubmed: 16622476
Oncol Rep. 2003 Nov-Dec;10(6):1777-82
pubmed: 14534695
Nat Rev Cancer. 2008 May;8(5):351-60
pubmed: 18418403
Cancer Sci. 2006 Jul;97(7):623-32
pubmed: 16827803
Nat Med. 2013 Apr;19(4):465-72
pubmed: 23455713
J Immunol Methods. 2004 Nov;294(1-2):15-22
pubmed: 15604012
Int Immunol. 2007 Oct;19(10):1223-34
pubmed: 17898045
Cancer Sci. 2005 Oct;96(10):695-705
pubmed: 16232202
Cancer Res. 2014 Feb 15;74(4):1045-55
pubmed: 24343228
Cancer Immunol Immunother. 2013 Apr;62(4):639-52
pubmed: 23143746
Tissue Antigens. 1996 Feb;47(2):93-101
pubmed: 8851721
Oncol Rep. 2014 Mar;31(3):1051-8
pubmed: 24366042
Cancer Sci. 2011 May;102(5):918-25
pubmed: 21281401
Biochem Biophys Res Commun. 2006 Apr 28;343(1):269-78
pubmed: 16540092
J Transl Med. 2013 Apr 04;11:88
pubmed: 23557172
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
J Immunother. 2013 Feb;36(2):133-51
pubmed: 23377668
Science. 2006 Oct 6;314(5796):126-9
pubmed: 16946036
Clin Cancer Res. 2015 Jan 15;21(2):312-21
pubmed: 25391695
N Engl J Med. 2013 Jul 11;369(2):134-44
pubmed: 23724846
Cancer Sci. 2019 Oct;110(10):3049-3060
pubmed: 31390678
Cancer Sci. 2010 Mar;101(3):594-600
pubmed: 20132220