Survivin (BIRC5) peptide vaccine in the 4T1 murine mammary tumor model: a potential neoadjuvant T-cell immunotherapy for triple negative breast cancer.

Abstract

A triple negative breast cancer (TNBC) model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin (SVN)-peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but minimal morbidity/mortality within the required study period. Later, in a second cohort of mice, the SVN-peptide microparticle vaccine was administered via intraperitoneal injection at study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3-4 days. Vaccination with SVN peptides was associated with a peptide antigen-specific {gamma}IFN Elispot response in the murine splenocyte population but was absent from the control microparticle group. At end of study, we found that vaccination with adjuvanted SVN-peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptide-less vaccination group. These studies suggest that T-cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for TNBC. More pre-clinical studies and clinical trials will be needed to explore this concept further.