Tumor vaccines

Stevenson, Freda K., Rice, Jason and Zhu, Delin (2004) Tumor vaccines. Advances in Immunology, 82, 49-103. (doi:10.1016/S0065-2776(04)82002-9).

Abstract

Tumor vaccines able to deliver specific antigen to the immune system are now available and are beginning to stand the test of performance in human subjects. Target antigens are being defined, and sophisticated methods to measure induced specific responses are available. Initially, therefore, outcome is measurable in terms of immune parameters, This allows rapid evaluation of one level of efficacy prior to assessing clinical value. Our task is to rouse immunity against weak or tolerizing tumor antigens, and, in order to succeed, we have to build vaccines that contain not only antigen, but also additional essential components. Adjuvants to activate innate immunity are clearly required, and the definition of the Toll-like receptors is opening possibilities for selective stimulation. Delivery of antigen to dendritic cells is a second goal and can be achieved either directly or via gene-based vaccines. Finally, there is a perceived need to activate high levels of T cell help to promote and maintain antibody, CD4+, or CD8+ effector pathways. The easiest way to build components into a vaccine is to use genetic technology, and therefore gene-based vaccines are likely to have a real future. Physical means to improve delivery and potential combinations with viral vector-mediated delivery may be required to optimize performance. Opportunities to codeliver genes encoding cytokines, chemokines, and other molecules are there. It will take time to exploit the new genetic information and technology, and tailoring of vaccines for specific target antigens will be required. Provided flexible and rapid evaluation in pilot clinical trials is allowed at reasonable cost, design will progress to the stage where tumor vaccines will be a reality. Vaccination of patients is litkely to succeed mainly in the setting of minimal residual disease. However, transfer of immunity from vaccinated donors of transplants, or from cells expanded in vitro, should also have a place. Vaccination could enhance the already successful passive immunotherapies being used to attack residual leukemic cells or dangerous viruses in immunosuppressed patients. A successful immune response should provide continuous surveillance against emergent tumor, and this would be a major contribution to the treatment of cancer.

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Contributors

Author: Freda K. Stevenson

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