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.

New modalities of cancer treatment for NSCLC: focus on immunotherapy

“…Mucinous glycoprotein-1 (MUC1) is another tumor-associated antigen that is commonly expressed in NSCLC, and often aberrantly expressed or glycosylated. 50 Two MUC1 vaccines, L-BLP25 and TG4010, have shown evidence of activity in clinical trials, and are being pursued in Phase III trials.…”

“…L-BLP25 (tecemotide, Stimuvax®) uses the BLP25 lipo-peptide of MUC1 and an adjuvant in a liposomal delivery system. 50 , 51 In a Phase IIb trial in patients with stage 3b or 4 NSCLC who were stable or had responded to first-line chemotherapy, L-BLP25 following a low dose of cyclophosphamide was associated with improved median and 2-year survival, particularly in the subset of patients with stage 3b locoregional disease. 51 Two trials will evaluate overall survival in patients with nonresectable stage 3 NSCLC receiving best supportive care with L-BLP25 versus placebo, following a low dose of cyclophosphamide.…”