Cytokines as Biologic Adjuvants

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Studies are ongoing to better define the role of exogenous cytokines in vaccine design and development. For these and other ongoing studies, several transgenic (Tg) mouse strains have been developed for vaccine therapy tumor models. These include Tg mice that express either CEA or MUC-1 as self-antigens at sites similar to those expressed in humans, and two Tg mouse strains that develop spontaneous tumors. Double Tg mouse strains have recently been developed in which spontaneous tumors arise that express either CEA or MUC-1 as self-antigen and in tumor tissue. Preclinical and clinical studies have now demonstrated the role of GM-CSF in vaccine therapy by recruitment of dendritic cells. Recombinant avipox viruses have now been developed that express GM-CSF as a transgene. When administered as a single injection, these vectors have recently been shown to enhance both the percentage and absolute number of APC (including dendritic cells) in the regional lymph nodes that drain the injection site. Both the magnitude and duration of this response was shown to be far greater than that achieved with the administration of four daily injections of recombinant GM-CSF protein. Recent studies have shown that the co-administration of recombinant avipox virus expressing CEA with recombinant avipox virus expressing GM-CSF significantly enhanced CEA-specific immunity, with an accompanying immunotherapeutic response in tumor-bearing CEA Tg mice. Studies are ongoing to use the new transgenic tumor models to better define novel vaccine strategies.