Oncolytic vesicular stomatitis virus-based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8+ T-cell functionality

Abstract

The occurrence of triple-negative breast cancer (TNBC) is significant, with an estimated 40,000 cases diagnosed in US women each year (American Cancer Society, 2018). TNBC is a vastly heterogeneous disease that are grouped together histologically since they lack hormone and Her-2 receptors. However, TNBC is best considered as an umbrella term, encompassing a wide spectrum of entities with distinct genetic, transcriptional, histological and clinical differences.1–3 As a group, TNBC is associated with high proliferation, early recurrence and poor survival rates.2 4 This aggressive disease is resistant to widely used targeted therapies such as trastuzumab and endocrine therapies, which have been effective at reducing breast cancer mortality. The best chance for survival is early detection, followed by neoadjuvant chemotherapy (NAC) and surgical resection.5 Patients with early-stage TNBC have increased rates of pathologic complete response (pCR) after NAC compared with other breast cancer subtypes. Indeed, the best prognostic factor for TNBC is the patient’s response to NAC. However, the increased pCR rates, but worse survival observed in TNBC—termed the triple negative paradox—appears to be driven by higher relapse rates among those patients whose tumors are not eradicated by chemotherapy.2 5 There are very limited and often ineffective treatment options for patients with poor prognosis (chemoresistant and late-stage/metastatic) TNBC.2