Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.
Animals
Antigens, Neoplasm
/ genetics
Breast Neoplasms
/ genetics
CD8-Positive T-Lymphocytes
/ drug effects
Cancer Vaccines
/ administration & dosage
Cell Line, Tumor
Female
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Immunotherapy
/ methods
Lymphocytes, Tumor-Infiltrating
/ drug effects
Mammary Neoplasms, Experimental
/ genetics
Mice
Mice, Transgenic
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Receptor, ErbB-2
/ genetics
Vaccines, Combined
/ administration & dosage
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
30
01
2020
revised:
17
04
2020
accepted:
25
06
2020
pubmed:
1
8
2020
medline:
26
11
2021
entrez:
1
8
2020
Statut:
ppublish
Résumé
Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers. Our models of HER2 We found that only vaccination targeting HER2Δ16, a driver of oncogenicity and HER2-therapeutic resistance, could elicit significant antitumor responses, while vaccines targeting a nondriver tumor-specific antigen or tumor neoepitopes did not. Vaccine-induced HER2-specific CD8 Combining oncogenic driver targeted vaccines with selective ICB offers a rational paradigm for precision immunotherapy, which we are clinically evaluating in a phase II trial (NCT03632941).
Identifiants
pubmed: 32732224
pii: 1078-0432.CCR-20-0389
doi: 10.1158/1078-0432.CCR-20-0389
pmc: PMC7483405
mid: NIHMS1609129
doi:
Substances chimiques
Antigens, Neoplasm
0
Cancer Vaccines
0
Immune Checkpoint Inhibitors
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Vaccines, Combined
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT03632941']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4670-4681Subventions
Organisme : NCI NIH HHS
ID : K22 CA212058
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA238217
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009111
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA100639
Pays : United States
Organisme : CIHR
ID : FND-148373
Pays : Canada
Organisme : NCI NIH HHS
ID : R01 CA098371
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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