Combination therapy with an OX40L fusion protein and a vaccine targeting the transcription factor twist inhibits metastasis in a murine model of breast cancer.

ABSTRACT: OX40 is a costimulatory receptor that potentiates proliferation, survival, memory formation, and effector function of CD4⁺ and CD8⁺ T-cells, while overcoming the suppressive activity of regulatory T-cells (Tregs). Here, we explored the combination of an OX40L fusion protein (OX40L-FP) with a poxvirus-based cancer vaccine (MVA-Twist-TRICOM) to inhibit tumor metastasis in the 4T1 murine breast cancer model. Contrary to the single agent treatments, the combination therapy significantly decreased the number of metastatic colonies per lung and prolonged survival. Depletion studies demonstrated that these effects were mediated by both CD4⁺ and CD8⁺ T-cells. The combination therapy a) increased the total number of T-cells in the CD4⁺Foxp3

SUBMITTER: Malamas AS 

PROVIDER: S-EPMC5710887 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature