Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer.
Aged
Antigens, Neoplasm
/ immunology
Cancer Vaccines
Dendritic Cells
/ immunology
Humans
Kaplan-Meier Estimate
Male
Membrane Proteins
/ immunology
Middle Aged
Mucin-1
/ immunology
Neoplasm Proteins
/ immunology
Prostatic Neoplasms, Castration-Resistant
/ immunology
Skin
/ immunology
T-Lymphocytes
/ immunology
Treatment Outcome
Vaccination
/ adverse effects
Castration-resistant prostate cancer
Dendritic cell vaccination
Immunotherapy
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
14 11 2019
14 11 2019
Historique:
received:
25
06
2019
accepted:
22
10
2019
entrez:
16
11
2019
pubmed:
16
11
2019
medline:
3
7
2020
Statut:
epublish
Résumé
Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC). We investigated the immunological response and clinical outcome of vaccination with blood-derived CD1c In this randomized phase IIa trial, 21 chemo-naive CRPC patients received maximally 9 vaccinations with mature mDCs, pDCs or a combination of mDCs plus pDCs. DCs were stimulated with protamine/mRNA and loaded with tumor-associated antigens NY-ESO-1, MAGE-C2 and MUC1. Primary endpoint was the immunological response after DC vaccination, which was monitored in peripheral blood and in T cell cultures of biopsies of post-treatment delayed-type hypersensitivity-skin tests. Main secondary endpoints were safety, feasibility, radiological PFS (rPFS) and overall survival. Radiological responses were assessed by MRIs and contrast-enhanced Both tetramer/dextramer-positive (dm Immunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome. ClinicalTrials.gov identifier NCT02692976, registered 26 February 2016, retrospectively registered.
Sections du résumé
BACKGROUND
Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC). We investigated the immunological response and clinical outcome of vaccination with blood-derived CD1c
METHODS
In this randomized phase IIa trial, 21 chemo-naive CRPC patients received maximally 9 vaccinations with mature mDCs, pDCs or a combination of mDCs plus pDCs. DCs were stimulated with protamine/mRNA and loaded with tumor-associated antigens NY-ESO-1, MAGE-C2 and MUC1. Primary endpoint was the immunological response after DC vaccination, which was monitored in peripheral blood and in T cell cultures of biopsies of post-treatment delayed-type hypersensitivity-skin tests. Main secondary endpoints were safety, feasibility, radiological PFS (rPFS) and overall survival. Radiological responses were assessed by MRIs and contrast-enhanced
RESULTS
Both tetramer/dextramer-positive (dm
CONCLUSIONS
Immunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT02692976, registered 26 February 2016, retrospectively registered.
Identifiants
pubmed: 31727154
doi: 10.1186/s40425-019-0787-6
pii: 10.1186/s40425-019-0787-6
pmc: PMC6854814
doi:
Substances chimiques
Antigens, Neoplasm
0
CTAG1B protein, human
0
Cancer Vaccines
0
MAGEC2 protein, human
0
MUC1 protein, human
0
Membrane Proteins
0
Mucin-1
0
Neoplasm Proteins
0
Banques de données
ClinicalTrials.gov
['NCT02692976']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
302Références
J Clin Oncol. 2008 Jan 10;26(2):242-5
pubmed: 18182665
Clin Cancer Res. 2016 May 1;22(9):2155-66
pubmed: 26712687
N Engl J Med. 2013 Jan 10;368(2):138-48
pubmed: 23228172
J Immunother Cancer. 2019 Jan 30;7(1):23
pubmed: 30700328
Blood. 2002 Dec 15;100(13):4512-20
pubmed: 12393628
J Natl Cancer Inst. 2010 Sep 22;102(18):1388-97
pubmed: 20826737
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
N Engl J Med. 2013 Jul 18;369(3):213-23
pubmed: 23863050
Nat Med. 2004 May;10(5):475-80
pubmed: 15122249
Lancet Oncol. 2015 Feb;16(2):152-60
pubmed: 25601341
J Immunother. 2007 Jan;30(1):1-15
pubmed: 17198079
J Immunother. 2016 Jul-Aug;39(6):241-8
pubmed: 27227325
Nature. 1998 Mar 19;392(6673):245-52
pubmed: 9521319
Clin Cancer Res. 2013 Mar 15;19(6):1525-33
pubmed: 23382117
Clin Cancer Res. 2000 Jun;6(6):2175-82
pubmed: 10873066
J Clin Oncol. 2016 Apr 20;34(12):1402-18
pubmed: 26903579
Expert Rev Clin Immunol. 2014 Jul;10(7):915-26
pubmed: 24758519
J Clin Oncol. 2013 Aug 10;31(23):2963-9
pubmed: 23835712
Cancer Res. 2013 Feb 1;73(3):1063-75
pubmed: 23345163
Front Immunol. 2014 May 06;5:191
pubmed: 24834066
Prostate. 2004 Jun 1;59(4):440-7
pubmed: 15065093
Oncoimmunology. 2015 Apr 1;4(8):e1019197
pubmed: 26405571
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
Blood. 2013 Aug 8;122(6):932-42
pubmed: 23794066
J Immunol. 2000 Dec 1;165(11):6037-46
pubmed: 11086035
J Clin Oncol. 2017 Oct 1;35(28):3198-3206
pubmed: 28809610
J Immunother. 2015 Feb-Mar;38(2):71-6
pubmed: 25658616
Cancer Immunol Immunother. 2015 Nov;64(11):1461-73
pubmed: 26275446
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Cancer Immunol Immunother. 2013 Jan;62(1):137-47
pubmed: 22865266
Immunity. 2013 Jul 25;39(1):38-48
pubmed: 23890062
N Engl J Med. 2014 Jul 31;371(5):424-33
pubmed: 24881730
Nature. 2014 Nov 27;515(7528):563-7
pubmed: 25428504
Lancet Oncol. 2008 Sep;9(9):850-6
pubmed: 18708295
J Natl Cancer Inst. 2017 Apr 1;109(4):
pubmed: 28376158
N Engl J Med. 2011 May 26;364(21):1995-2005
pubmed: 21612468
N Engl J Med. 2004 Oct 7;351(15):1513-20
pubmed: 15470214
Trends Immunol. 2015 Apr;36(4):265-76
pubmed: 25797516
J Clin Oncol. 2005 Aug 20;23(24):5779-87
pubmed: 16110035
Eur Urol. 2014 Feb;65(2):467-79
pubmed: 24321502
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018 Jan;10(1):
pubmed: 28382713
J Clin Oncol. 2019 May 1;37(13):1051-1061
pubmed: 30817251
Lancet. 2010 Oct 2;376(9747):1147-54
pubmed: 20888992
Cancer Res. 2012 Dec 1;72(23):6102-10
pubmed: 23010076
J Exp Med. 2006 Jul 10;203(7):1629-35
pubmed: 16785312
Oncotarget. 2016 Aug 16;7(33):52810-52817
pubmed: 27429197
Oncoimmunology. 2016 Sep 2;5(10):e1227902
pubmed: 27853652
J Clin Oncol. 2017 Jan;35(1):40-47
pubmed: 28034081
N Engl J Med. 2004 Oct 7;351(15):1502-12
pubmed: 15470213
Lancet Oncol. 2017 Mar;18(3):e143-e152
pubmed: 28271869
Eur Urol. 2017 Feb;71(2):151-154
pubmed: 27477525
Lancet Oncol. 2014 Jun;15(7):700-12
pubmed: 24831977
J Clin Oncol. 2008 Mar 1;26(7):1148-59
pubmed: 18309951
Nature. 2017 May 4;545(7652):60-65
pubmed: 28397821
Nat Immunol. 2018 Feb;19(2):108-119
pubmed: 29348500
Oncotarget. 2016 Dec 13;7(50):83115-83133
pubmed: 27825118
Lancet Oncol. 2012 Oct;13(10):983-92
pubmed: 22995653
J Nucl Med. 2015 May;56(5):668-74
pubmed: 25791990
N Engl J Med. 2010 Jul 29;363(5):411-22
pubmed: 20818862
J Immunother Cancer. 2019 Apr 18;7(1):109
pubmed: 30999964
N Engl J Med. 2012 Sep 27;367(13):1187-97
pubmed: 22894553
Ann Oncol. 2012 Sep;23 Suppl 8:viii47-52
pubmed: 22918928
Blood. 2009 Apr 30;113(18):4232-9
pubmed: 19176317
PLoS One. 2011;6(7):e21366
pubmed: 21754986
Ann Oncol. 2018 Aug 1;29(8):1620-1622
pubmed: 29992258