Poly-specific neoantigen-targeted cancer vaccines delay patient derived tumor growth.
Affinity
Cancer vaccine
Electroporation
Immunotherapy
Neoantigen
T cells
Vaccination
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
14 Feb 2019
14 Feb 2019
Historique:
received:
18
12
2018
accepted:
06
02
2019
entrez:
16
2
2019
pubmed:
16
2
2019
medline:
30
5
2019
Statut:
epublish
Résumé
Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine. In an effort to develop potent and efficacious neoantigen-based vaccines, we have developed different neoantigen minigene (NAM) vaccine vectors to determine the rules for a successful neoantigen cancer vaccine (NCV) delivered by plasmid DNA and electroporation. Immune responses were analyzed at the level of single neoantigen by flow cytometry and correlated with tumor growth. Adoptive T cell transfer, from HLA-2.1.1 mice, was used to demonstrate the efficacy of the NCV pipeline against human-derived tumors. In agreement with previous bodies of evidence, immunogenicity was driven by predicted affinity. A strong poly-functional and poly-specific immune response was observed with high affinity neoantigens. However, only a high poly-specific vaccine vector was able to completely protect mice from subsequent tumor challenge. More importantly, this pipeline - from the selection of neoantigens to vaccine design - applied to a new model of patient derived tumor xenograft resulted in therapeutic treatment. These results suggest a feasible strategy for a neoantigen cancer vaccine that is simple and applicable for clinical developments.
Sections du résumé
BACKGROUND
BACKGROUND
Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine.
METHODS
METHODS
In an effort to develop potent and efficacious neoantigen-based vaccines, we have developed different neoantigen minigene (NAM) vaccine vectors to determine the rules for a successful neoantigen cancer vaccine (NCV) delivered by plasmid DNA and electroporation. Immune responses were analyzed at the level of single neoantigen by flow cytometry and correlated with tumor growth. Adoptive T cell transfer, from HLA-2.1.1 mice, was used to demonstrate the efficacy of the NCV pipeline against human-derived tumors.
RESULTS
RESULTS
In agreement with previous bodies of evidence, immunogenicity was driven by predicted affinity. A strong poly-functional and poly-specific immune response was observed with high affinity neoantigens. However, only a high poly-specific vaccine vector was able to completely protect mice from subsequent tumor challenge. More importantly, this pipeline - from the selection of neoantigens to vaccine design - applied to a new model of patient derived tumor xenograft resulted in therapeutic treatment.
CONCLUSIONS
CONCLUSIONS
These results suggest a feasible strategy for a neoantigen cancer vaccine that is simple and applicable for clinical developments.
Identifiants
pubmed: 30764846
doi: 10.1186/s13046-019-1084-4
pii: 10.1186/s13046-019-1084-4
pmc: PMC6376688
doi:
Substances chimiques
Antigens, Neoplasm
0
Cancer Vaccines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
78Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 17827
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 15216
Références
Protein Sci. 2003 May;12(5):1007-17
pubmed: 12717023
Int J Cancer. 2005 Nov 10;117(3):444-55
pubmed: 15906358
Eur J Immunol. 2006 May;36(5):1337-49
pubmed: 16619291
Mol Ther. 2010 Aug;18(8):1559-67
pubmed: 20531395
Cancer Res. 2012 Mar 1;72(5):1081-91
pubmed: 22237626
Mol Cancer. 2012 Apr 19;11:22
pubmed: 22515704
Oncoimmunology. 2014 Jan 1;3(1):e27529
pubmed: 24790791
J Exp Med. 2014 Oct 20;211(11):2231-48
pubmed: 25245761
N Engl J Med. 2014 Dec 4;371(23):2189-2199
pubmed: 25409260
Nature. 2014 Nov 27;515(7528):572-6
pubmed: 25428506
Science. 2015 May 15;348(6236):803-8
pubmed: 25837513
Lancet Oncol. 2015 May;16(5):522-30
pubmed: 25840693
Nature. 2015 Apr 30;520(7549):692-6
pubmed: 25901682
Mol Med Rep. 2015 Nov;12(5):7479-84
pubmed: 26397140
J Transl Med. 2016 Feb 29;14:61
pubmed: 26928703
Science. 2016 Mar 25;351(6280):1463-9
pubmed: 26940869
PLoS One. 2016 May 18;11(5):e0155189
pubmed: 27192170
Science. 2016 Jun 10;352(6291):1337-41
pubmed: 27198675
Nature. 2016 Jun 01;534(7607):396-401
pubmed: 27281205
Nat Commun. 2016 Nov 21;7:13404
pubmed: 27869121
Nat Mater. 2017 Apr;16(4):489-496
pubmed: 28024156
Nat Immunol. 2017 Feb 15;18(3):255-262
pubmed: 28198830
Nat Rev Cancer. 2017 Apr;17(4):209-222
pubmed: 28233802
Nature. 2017 Jul 13;547(7662):217-221
pubmed: 28678778
Nature. 2017 Jul 13;547(7662):222-226
pubmed: 28678784
Nature. 2017 Nov 23;551(7681):512-516
pubmed: 29132146
Nat Rev Immunol. 2018 Mar;18(3):168-182
pubmed: 29226910
EMBO Rep. 2018 Mar;19(3):
pubmed: 29367285
Nat Commun. 2018 Mar 15;9(1):1092
pubmed: 29545564
N Engl J Med. 2018 May 10;378(19):1789-1801
pubmed: 29658430
J Exp Clin Cancer Res. 2018 Apr 20;37(1):86
pubmed: 29678194
Sci Rep. 2018 Aug 24;8(1):12735
pubmed: 30143704