Cytokines as Biologic Adjuvants

目前正在进行研究，以更好地确定外源性细胞因子在疫苗设计和开发中的作用。对于这些和其他正在进行的研究，已经开发了几种转基因（Tg）小鼠品系用于疫苗治疗肿瘤模型。其中包括在与人类相似的位点表达CEA或MUC-1作为自身抗原的Tg小鼠，以及两种产生自发肿瘤的Tg小鼠品系。双Tg小鼠品系最近被开发出来，在肿瘤组织中表达CEA或MUC-1作为自身抗原的自发性肿瘤。

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.