An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice

A DNA vaccine encoding human carcinoembryonic antigen (CEA) broke periphera l T-cell tolerance toward this tumor self-antigen expressed by Lewis lung c arcinoma stably transduced with CEA in C57BL/6J mice transgenic for CEA. Th is vaccine, delivered by oral gavage with an attenuated strain of Salmonell a typhimurium (SL7207), and boosted with an antibody-IL2 fusion protein, in duced tumor-protective immunity mediated by MHC class I anti gen-restricted CD8(+) T cells, resulting in eradication of subcutaneous tumors in 100% of mice and prevention of experimental pulmonary metastases in 75% of experim ental animals. Both CTL and antigen-presenting dendritic cells were activat ed as indicated by a decisive increase in their respective activation marke rs CD2, CD25, CD28 as well as CD48 and CD80. The antitumor effects of this CEA-based DNA vaccine obtained in prophylactic settings, suggest that this approach could lead to the rational design of effective treatment modalitie s for human lung cancer. (C) 2001 Elsevier Science Ltd. All rights reserved .