Naylor Paul H, Hadden John W
Immuno-Rx Inc., Broad Hollow BioScience Park, 1 BioScience Park Drive, Farmingdale, NY 11735, USA.
Int Immunopharmacol. 2003 Aug;3(8):1205-15. doi: 10.1016/S1567-5769(03)00025-0.
Given the critical role of cell-mediated immunity (CMI) in defense against attack from pathogens that establish chronic infections, it has become abundantly clear that current vaccine methodology will not be sufficient to develop the appropriate immune response for protection and/or clearance of infection. By extension, this logic also applies to cancer vaccines where T cell immune-mediated destruction is a critical mechanism for control of the disease. This review describes our current thoughts on the events associated with immune activation and evaluates the various approaches to achieve successful immune activation with defined or targeted antigens as opposed to using inactivated or attenuated organisms. The advantages and disadvantages of the current adjuvants for antigens that focus on mimicking the infection events via the innate immune system or antigen uptake are described in the context of generation of T cell specific responses. A central theme of the discussions is the importance of cytokines in modulating the immune response towards T cell immunity, either by adjuvant modulation or use of natural cytokine mixtures targeted towards the site of immune activation. Also discussed is the possibility that thymomimetic agents such as thymosin alpha1, levamisole and methyl inosine monophosphate (MIMP) may be useful in enhancing the T cell mediated arm of the immune response.
鉴于细胞介导的免疫（CMI）在抵御建立慢性感染的病原体攻击中发挥着关键作用，目前已非常明确的是，当前的疫苗方法不足以产生适当的免疫反应来保护和/或清除感染。由此类推，这一逻辑也适用于癌症疫苗，其中T细胞免疫介导的破坏是控制该疾病的关键机制。本综述描述了我们目前对与免疫激活相关事件的看法，并评估了与使用灭活或减毒生物体相反，利用明确或靶向抗原实现成功免疫激活的各种方法。在产生T细胞特异性反应的背景下，描述了当前用于抗原的佐剂的优缺点，这些佐剂侧重于通过先天免疫系统或抗原摄取来模拟感染事件。讨论的一个中心主题是细胞因子在调节针对T细胞免疫的免疫反应中的重要性，这可以通过佐剂调节或使用靶向免疫激活部位的天然细胞因子混合物来实现。还讨论了胸腺模拟剂如胸腺素α1、左旋咪唑和单磷酸甲基次黄嘌呤（MIMP）可能有助于增强免疫反应中T细胞介导分支的可能性。
