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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.

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The Wistar Institute, Vaccine and Immunotherapy Center, Philadelphia, Pennsylvania.
MedGenome Inc., Foster City, California.
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
Geneos Therapeutics, Plymouth Meeting, Pennsylvania.
The Wistar Institute, Vaccine and Immunotherapy Center, Philadelphia, Pennsylvania.
Contributed equally


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.

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