Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.

ABSTRACT:

Purpose

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.

Experimental design

Our models of HER2⁺ breast cancer exhibit molecular signatures that are reflective of advanced human HER2⁺ breast cancer, with a small numbers of neoepitopes and elevated immunosuppressive markers. Using these, we vaccinated against the oncogenic HER2Δ16 isoform, a nondriver tumor-associated gene (GFP), and specific neoepitopes. We

SUBMITTER: Crosby EJ 

PROVIDER: S-EPMC7483405 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature