Autologous Dendritic Cell Vaccines in Non-Small Cell Lung Cancer

Tumor vaccines may have a role in treatment of both advanced and limited stage lung cancer. Vaccines are intended to enhance antitumor immune responses. This proposal is built around the use of Dendritic Cells (DC), one of the most potent components of the immune response, as part of the vaccine. Responses to vaccines may however vary, and examination of the relative efficacy in individuals with different stages of lung cancer will be important for defining the potential of this approach. One concern is that cellular vaccines delivered into the tumor environment may be significantly suppressed by tumor-derived factors known to be present in the cancer environment. Modifying the host environment either by removing tumor or with pharmacological agents, specifically COX-2 inhibitors (Celebrex@), may enhance antitumor responses to DC vaccines. To address these questions, this proposal will compare immune responses to DC vaccines in two target groups of lung cancer patients. The first year of the proposal will focus the on the relevant differences in immune response between stage 3 non-small cell lung cancer (NSCLC) and fully resected NSCLC patients to define the importance of tumor derived factors in generating an antitumor response. If major differences are apparent, the second year of the proposal will incorporate pharmacological manipulation of the host environment with COX-2 inhibitors to enhance responses to vaccines in stage 3 NSCLC. In this context, the study will explore the effects of NSCLC tumor environment on immune reactivity to a therapeutically relevant vaccine, and to evaluate approaches to enhance NSCLC-antigen specific lymphocyte responses in vivo. Correlative studies will define whether poor responses to vaccines can be predicted by plasma levels of the tumor derived factor PGE-2 as a nonspecific markers of immuno-suppression and perhaps suggest who might most benefit from pharmacological intervention to complement tumor vaccines.