Paracrine cytokine adjuvants in cancer immunotherapy.

Advances in our understanding of the molecular events of antigen recognition by T cells and T cell activation are opening up new approaches to cancer immunotherapy. The identification and cloning of cytokines provide one important set of tools for manipulating immunologic responses. For cancer therapy, cytokines such as interleukin-2 have been administered systemically. However, systemic administration of cytokines ignores the paracrine nature of their action. Recently, an alternative approach has been explored that produces high concentrations of cytokines local to the tumor cells. This is achieved either by transduction of the tumor cells with the cytokine gene or by mixture of the tumor cells with cytokine containing biodegradable polymer microspheres. Under these circumstances, the locally released cytokine produces a strong local inflammatory response specific to the particular cytokine. In some cases, a potent tumor-specific T cell response results, capable of mediating regression of systemic tumor deposits. This paracrine delivery of cytokines can therefore be considered as a new type of adjuvant in the design of vaccines for cancer as well as microbial infections.