Cytokines as Biologic Adjuvants

研究正在进行中，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。这些包括在与人类中表达的位点相似的位点表达CEA或MUC-1作为自身抗原的Tg小鼠，以及发展自发性肿瘤的两种Tg小鼠品系。最近已经开发了双Tg小鼠品系，其中自发性肿瘤出现，其表达CEA或MUC-1作为自身抗原和在肿瘤组织中。 临床前和临床研究现已证明GM-CSF通过募集树突状细胞在疫苗治疗中的作用。现在已经开发了表达GM-CSF作为转基因的重组禽痘病毒。当作为单次注射给药时，这些载体最近已显示出提高了排出注射部位的区域淋巴结中APC（包括树突细胞）的百分比和绝对数量。研究表明，这种反应的幅度和持续时间都远大于每天注射四次重组GM-CSF蛋白所达到的效果。最近的研究表明，表达CEA的重组禽痘病毒与表达GM-CSF的重组禽痘病毒的共施用显著增强CEA特异性免疫，在荷瘤CEA Tg小鼠中伴随免疫应答。正在进行研究，以使用新的转基因肿瘤模型来更好地定义新的疫苗策略。

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.