Current status of adoptive immunotherapy of cancer

Abstract

The sentinel observations made by William B. Coley, M.D. in the 1890s that patients with malignancies can respond to the intratumoral inoculation of live bacterial organisms or bacterial toxins became the cornerstone for the development of immunotherapy for cancers. It has been repeatedly demonstrated that tumors express unique proteins which can trigger an immune response. The adoptive transfer of immune cells to the host with established malignancy can mediate complete eradication of local or disseminated tumors and result in systemic immunity. This review summarizes the current experimental as well as clinical status of adoptive immunotherapy of cancer. There are a number of different methods to isolate tumor-reactive T cells from the tumor-bearing host and allow for their ex vivo expansion. A new direction in this field includes attempts to up-regulate the immunogenicity of tumors by genetically modifying tumor cells to express immunoregulatory peptides (i.e. cytokines, co-stimulatory molecules, etc.) in order to exploit endogenously weak immune responses to autochthonous tumors. Other new directions involve developing methods to generate or isolate tumor-reactive T cells subsets by selective in vitro stimulation (i.e. bacterial superantigens) or genetic engineering of activated T cells to enhance their ability to mediate tumor destruction. Although adoptive immunotherapy has thus far added little to the routine treatment of human cancer, it is likely that continued efforts at defining the elements involved in T cell recognition and destruction of tumor cells will broaden the applicability of T cells as important therapeutic reagents.