Targeting the immune system in non-small-cell lung cancer: bridging the gap between promising concept and therapeutic reality.
Developing effective immunotherapy for lung cancer is a daunting but hugely attractive challenge. Until recently, non-small-cell lung cancer (NSCLC) was thought of as a nonimmunogenic tumor, but there is now evidence highlighting the integral role played by both inflammatory and immunologic responses in lung carcinogenesis. Despite recent encouraging preclinical and phase I/II data, there are a paucity of phase III trials showing a clear clinical benefit for vaccines in lung cancer. There are many difficulties to overcome before the development of a successful therapy. Perhaps a measurable immune response may not translate into a clinically meaningful or radiologic response. Patient selection may also be a problem for ongoing clinical studies. The majority of trials for lung cancer vaccines are focused on patients with an advanced stage of the disease; however, the ideal candidates may be patients with a lower tumor burden and stage I or II disease. Selecting the exact antigens to target is also difficult. It will likely require multiple epitopes of a diverse set of genes restricted to multiple haplotypes to generate a truly effective vaccine that is able to overcome the various immunologic escape mechanisms that tumors use. This review discusses the most promising active immunotherapy using protein/peptide vaccines, whole cell vaccines, and dendritic cell vaccines and examines current phase I and II clinical trial data on some novel nonspecific immunomodulating agents.
Kelly
Ronan J
RJ
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Gulley
James L
JL
Giaccone
Giuseppe
G
D019496:Cancer Vaccines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007107:Immune System / Q000502:physiology; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D019496:Cancer Vaccines