Format

Send to

Choose Destination
Cancer Immunol Res. 2019 Feb;7(2):174-182. doi: 10.1158/2326-6066.CIR-18-0283. Epub 2019 Jan 24.

A Synthetic DNA, Multi-Neoantigen Vaccine Drives Predominately MHC Class I CD8+ T-cell Responses, Impacting Tumor Challenge.

Author information

1
The Wistar Institute, Vaccine and Immunotherapy Center, Philadelphia, Pennsylvania.
2
MedGenome Inc., Foster City, California.
3
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
4
Geneos Therapeutics, Plymouth Meeting, Pennsylvania.
5
The Wistar Institute, Vaccine and Immunotherapy Center, Philadelphia, Pennsylvania. dweiner@wistar.org.
#
Contributed equally

Abstract

T-cell recognition of cancer neoantigens is important for effective immune-checkpoint blockade therapy, and an increasing interest exists in developing personalized tumor neoantigen vaccines. Previous studies utilizing RNA and long-peptide neoantigen vaccines in preclinical and early-phase clinical studies have shown immune responses predominantly driven by MHC class II CD4+ T cells. Here, we report on a preclinical study utilizing a DNA vaccine platform to target tumor neoantigens. We showed that optimized strings of tumor neoantigens, when delivered by potent electroporation-mediated DNA delivery, were immunogenic and generated predominantly MHC class I-restricted, CD8+ T-cell responses. High MHC class I affinity was associated specifically with immunogenic CD8+ T-cell epitopes. These DNA neoantigen vaccines induced a therapeutic antitumor response in vivo, and neoantigen-specific T cells expanded from immunized mice directly killed tumor cells ex vivo These data illustrate a unique advantage of this DNA platform to drive CD8+ T-cell immunity for neoantigen immunotherapy.

PMID:
30679156
PMCID:
PMC6622455
[Available on 2020-02-01]
DOI:
10.1158/2326-6066.CIR-18-0283

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center