Non-small-cell lung cancer usually carries a dismal prognosis. Novel treatment approaches are clearly warranted.
Immunotherapy has emerged as a promising area of research developing agents that manipulate the immune system to induce antitumor responses while avoiding major toxicity. New
vaccines and checkpoint inhibitors are currently undergoing investigation in phase II and phase III clinical trials. In advanced
non-small-cell lung cancer (NSCLC),
belagenpumatucel-L, an allogeneic cell
vaccine directed against
transforming growth factor β in the tumor microenvironment, knocks down the immune suppression caused by the
tumor and has demonstrated a dose- and time-dependent efficacy in some subgroups of patients.
L-BLP25 and
TG4010 are both antigenic
vaccines that target
mucin 1, whose encoding proto-oncogene is commonly mutated in solid
tumors. The
L-BLP25 vaccine achieved a significant improvement in overall survival in the subgroup of patients with stage IIIB NSCLC treated with
chemoradiotherapy.
TG4010 vaccination resulted in better progression-free survival when added to
cisplatin-
gemcitabine chemotherapy. These results are being addressed in the currently ongoing phase III TIME trial. In the adjuvant setting, MAGE-A3, an
antigen-based
vaccine, showed promising results in
melanoma-associated
antigen A3 positive
lung cancer patients who underwent resection in the phase II study; however, no improvement in progression-free survival was observed in the phase III MAGRIT study. CIMAVax is a recombinant human
epidermal growth factor (
EGF)
vaccine that induces anti-
EGF antibody production and prevents
EGF from binding to its receptor. It has improved overall survival in patients with advanced NSCLC who achieve seroconversion.
Ipilimumab, an
immune checkpoint inhibitor that targets
cytotoxic T-lymphocyte antigen 4, demonstrated improved progression-free survival in advanced NSCLC patients who received the
drug after
chemotherapy in a phased regimen. Finally, anti-programmed
death receptor 1 agents have achieved durable response rates in phase I studies. This review gives an overview of the current data and the most promissory immunotherapeutic agents for NSCLC.