A Multicenter Pilot Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung Cancer

Vaccines targeting antigens aberrantly expressed on lung cancers and their precursors offer the potential for a relatively non-invasive prevention strategy. Worldwide, lung cancer remains the most important cause of cancer-related mortality, and an immunoprevention approach, if successful, has the potential to save many lives by prevention of lung cancer. All epithelial tumors, including lung cancer, express high levels of abnormal mucin (MUC)1 and MUC1-based therapeutic vaccines can increase this immune response to aberrant expressed MUC1 to therapeutic levels.We conducted a multicenter trial to evaluate the immunogenicity and safety of a MUC1 preventive vaccine in individuals with a significant smoking history and at high risk of developing lung cancer. The MUC1 vaccine was safe and elicited an immune response in 13%, which was lower than anticipated. Unexpectedly, we observed a high level of immune suppression in this cohort of heavy smokers, which has been previously documented in individuals who already have lung cancer. Although immunoprevention strategies are promising for reducing the risk of lung cancer in current and former heavy smokers, the immune environment induced by smoking, and the factors that drive immunosuppression are crucial barriers that must be overcome by well-designed immunoprevention strategies for lung cancer.