Active-specific immunotherapy for non-small cell lung cancer

Non-small cell lung cancer constitutes about 85% of all newly diagnosed cases of lung cancer and continues to be the leading cause of cancer-related deaths worldwide. Standard treatment for this devastating disease, such as systemic chemotherapy, has reached a plateau in effectiveness and comes with considerable toxicities. For all stages of disease fewer than 20% of patients are alive 5 years after diagnosis; for metastatic disease the median survival is less than one year. Until now, the success of active-specific immunotherapy for all tumor types has been sporadic and unpredictable. However, the active-specific stimulation of the host's own immune system still holds great promise for achieving non-toxic and durable antitumor responses. Recently, sipuleucel-T (Provenge(®); Dendreon Corp., Seattle, WA) was the first therapeutic cancer vaccine to receive market approval, in this case for advanced prostate cancer. Other phase III clinical trials using time-dependent endpoints, e.g. in melanoma and follicular lymphoma, have recently turned out positive. More sophisticated specific vaccines have now also been developed for lung cancer, which, for long, was not considered an immune-sensitive malignancy. This may explain why advances in active-specific immunotherapy for lung cancer lag behind similar efforts in renal cell cancer, melanoma or prostate cancer. However, various vaccines are now being evaluated in controlled phase III clinical trials, raising hopes that active-specific immunotherapy may become an additional effective therapy for patients with lung cancer. This article reviews the most prominent active-specific immunotherapeutic approaches using protein/peptide, whole tumor cells, and dendritic cells as vaccines for lung cancer.