Enhancing cancer vaccines with immunomodulators.

Harnessing the immune system to control cancer has been a challenge for cancer immunotherapists for many years. However, while specific immune responses to tumour-associated antigenic targets have been successfully induced in some patients, these responses have not always been sufficient to reproducibly and consistently mediate useful anti-tumour clinical activity. Many checks and balances have been incorporated into the immune response by nature to prevent or reduce the likelihood of autoimmunity or exaggerated protective inflammatory responses. Tolerance to self-antigens expressed on tumours is a major limitation in generating functional anti-tumour responses. In recent years, many of the pathways that mediate this tolerance have been identified, and reagents that can be used to manipulate these pathways have been clinically evaluated. These include: (a) pathways to activate professional antigen presenting cells, such as through Toll-like receptors, growth factors, such as GM-CSF, and the CD40 pathway; (b) use of cytokines, such as IL-2, IL-12, and Interferon alpha to enhance immune activation; and (c) pathways that inhibit T cell inhibitory signals, or Tregs. This article reviews clinical trials that have evaluated these approaches, and highlights promising combination vaccine/immunomodulator combination treatments based upon published clinical trial results.