Lentiviral vector followed by protein immunisation breaks tolerance against the self-antigen Her1 and results in lung cancer immunotherapy

Abstract

Background: Lung cancer remains a leading cause of cancer mortality, and so the aim of the present study was to develop a therapeutic vaccine protocol.

Methods: We constructed a lentiviral vector (LV) expressing the extracellular domain (ECD) of murine Her1, an antigen associated with poor prognosis in lung cancer.

Results: A single LV injection, followed by two Her1 protein boosts, was effective in reducing the metastatic burden of Lewis lung carcinoma in mice. The Her1 LV immunisation generated CD8+ T cells that recognised Her1 ECD presented by dendritic cells, and that also homed to Her1-expressing tumours. Protein boosting further increased the CD8+ T cell response and generated anti-Her1 antibodies; in the antibody response, Her1 LV priming increased Th1-dependent immunoglobulin G2c production.

Conclusions: The ability of this vaccine protocol to break both T cell and B cell tolerance to a self-antigen likely explains its effectiveness.