Chikh Ghania, Schutze-Redelmeier Marie-Paule
British Columbia Cancer Research Center, Dept of Advanced Therapeutics, Vancouver, Canada.
Biosci Rep. 2002 Apr;22(2):339-53. doi: 10.1023/a:1020151025412.
The induction of strong and long lasting T-cell response, CD4+ or CD8+, is a major requirement in the development of efficient vaccines. An important aspect involves delivery of antigens to dendritic cells (DCs) as antigen presenting cells (APCs) for the induction of potent antigen-specific CD8+ T lymphocyte (CTLs) responses. Protein or peptide-based vaccines become an attractive alternative to the use of live cell vaccines to stimulate CTL responses for the treatment of viral diseases or malignancies. However, vaccination with proteins or synthetic peptides representing discrete CTL epitopes have failed in most instances due to the inability for exogenous antigens to be properly presented to T cells via major histocompatibility complex (MHC) class I molecules. Modern vaccines, based on either synthetic or natural molecules, will be designed in order to target appropriately professional APCs and to co-deliver signals able to facilitate activation of DCs. In this review, we describe the recent findings in the development of lipid-based formulations containing a combination of these attributes able to deliver tumor- or viral-associated antigens to the cytosol of DCs. We present in vitro and pre-clinical studies reporting specific immunity to viral, parasitic infection and tumor growth.
诱导强烈且持久的T细胞应答，无论是CD4+还是CD8+，是高效疫苗研发的主要要求。一个重要方面涉及将抗原递送至作为抗原呈递细胞（APC）的树突状细胞（DC），以诱导强效的抗原特异性CD8+ T淋巴细胞（CTL）应答。基于蛋白质或肽的疫苗成为使用活细胞疫苗刺激CTL应答以治疗病毒性疾病或恶性肿瘤的有吸引力的替代方案。然而，在大多数情况下，用代表离散CTL表位的蛋白质或合成肽进行疫苗接种均告失败，原因是外源性抗原无法通过主要组织相容性复合体（MHC）I类分子正确呈递给T细胞。基于合成或天然分子的现代疫苗将被设计用于靶向合适的专职APC，并共同递送能够促进DC激活的信号。在本综述中，我们描述了在开发基于脂质的制剂方面的最新发现，这些制剂具有将肿瘤或病毒相关抗原递送至DC胞质溶胶的这些属性的组合。我们展示了体外和临床前研究，报告了对病毒、寄生虫感染和肿瘤生长的特异性免疫。
