Lung Cancer Prevention Through Prophylactic Vaccination Against Endogenous Retroviral Antigens.

摘要

No form of disease prevention has had greater success than prophylactic immunization. Whereas therapeutic cancer vaccines have only marginal evidence of clinical efficacy, prophylactic vaccination against tumor- associated antigens can confer life-long protection in both transplantable and transgenic cancer models. Yet most non-virally associated cancers lack candidate antigens that could be targeted for human cancer prevention. Endogenous Retroviral sequences and other transposable elements (TEs) comprise almost 40% of the human genome. These remnants of exogenous retroviruses are crippled through mutation and do not make infectious virus. Furthermore, promoter and histone modification silence their expression. Nevertheless, many cancers express them as a result of altered gene regulation, and the proteins they encode are recognizable as neo-antigens in both mouse and man. We have created repeat sequence arrays for the mouse and human genomes. Using mouse lung cancer models and human clinical samples, we are defining the pattern and kinetics of TE expression during neoplastic transformation. We seek to determine if endogenous immune responses to such antigens may lead to early detection, and if prophylactic vaccination delays or prevents the onset of lung cancer in mouse models.