Targeting the immune system for management of NSCLC: the revival?

Abstract

Immunotherapy, based on increasing knowledge of the mechanisms of immune-mediated elimination of tumor cells, is a new approach to lung cancer therapy. This paper reviews clinical experience of two types of immunotherapy for lung cancer. In the first approach antigen-independent immunomodulatory therapy is used to target crucial immune checkpoints. This strategy includes use of ipilimumab—to block the interaction of cytotoxic T-lymphocyte antigen-4 with CD80 and/or CD86, thereby enhancing T-cell proliferation—and the fully human monoclonal antibodies BMS-936558 and BMS-936559—to target the programmed cell death protein 1 signaling pathway, thereby enhancing T-cell proliferation, cytokine secretion, and cytolysis of target cells. The second approach is antigen-specific cancer immunotherapy, including vaccines against melanoma-associated antigen 3, mucinous glycoprotein-1, transforming growth factor-beta 2, epidermal growth factor, and, less specifically, whole-tumor cell extracts. An overview of the clinical data from these strategies is presented, with discussion of questions and issues that remain unanswered.