Integrating bench with bedside: the role of vaccine therapy in the treatment of solid tumors. Clinical Oncology

摘要

The treatment of solid tumors continues to be one of the major challenges facing both patients and the oncology community. An improved understanding of how the immune system recognizes and eradicates tumor cells has led to an intense interest in therapeutic vaccine development, representing one of the most successful applications of bench-to-bedside translational research. Extensive "proof of principle" evidence from the bench has used murine models to demonstrate that active immunization can mediate effective tumor treatment. In 1991, a vaccine strategy employing recombinant vaccinia virus engineered to express carcinoembryonic antigen (CEA) was reported.2 Initial animal experiments documented the ability of vaccinia-CEA to induce humoral and cellular immunity by targeting a commonly expressed solid tumor antigen in a highly immunogenic vaccine-a result since confirmed in transgenic mice and in vitro experiments with human T cells. The first clinical trial with this vaccine was published in 1996, and numerous other studies, largely phase I in format, were conducted throughout the last 8 years, demonstrating the safety and feasibility of various poxvirus vaccines in patients with advanced solid tumors. While these studies were not designed or powered to determine clinical effectiveness, intriguing anecdotal evidence suggested that vaccination induced CEA-specific T cells, and even objective clinical responses, in some patients.