Gitlitz B J, Belldegrun A S, Figlin R A
Department of Medicine, University of California, School of Medicine, Los Angeles 90095-7059, USA.
Semin Urol Oncol. 2001 May;19(2):141-7.
The concept of tumor vaccines is not new. However, advances in gene transfer technology, tumor immunology, molecular biology, and methods of monitoring antitumor response, have allowed for novel, more specific vaccine approaches. For example, first-generation tumor vaccines were composed of whole inactivated cancer cells, or tumor lysates (Tuly) given together with immune adjuvants like bacillus Calmette-Guerin (BCG). Current strategies include tumor cells modified with genes encoding molecules necessary to stimulate a cytotoxic T cell response, such as cytokine genes, foreign HLA genes, tumor-associated antigen (TAA) genes, and even costimulatory molecules. Activation of cellular immunity requires at least three synergistic signals including presentation of specific tumor antigens, costimulatory signals (B7 molecules), and propagation of the immune response via cytokine release. In general, tumor cells often fail to demonstrate any of these immunostimulatory properties. Dendritic cell-based vaccines are gaining popularity as these cells can properly present TAA to the immune system, thus circumventing the poor antigen-presenting qualities of tumor cells. Dendritic cells can be "loaded" with TAA or other molecules either by their natural endocytotic capabilities, or by genetic modification.
肿瘤疫苗的概念并不新颖。然而，基因转移技术、肿瘤免疫学、分子生物学以及监测抗肿瘤反应方法的进展，使得新型、更具特异性的疫苗方法成为可能。例如，第一代肿瘤疫苗由完整的灭活癌细胞或肿瘤裂解物（Tuly）与免疫佐剂如卡介苗（BCG）一起组成。当前的策略包括用编码刺激细胞毒性T细胞反应所需分子的基因修饰肿瘤细胞，如细胞因子基因、外源HLA基因、肿瘤相关抗原（TAA）基因，甚至共刺激分子。细胞免疫的激活至少需要三个协同信号，包括特定肿瘤抗原的呈递、共刺激信号（B7分子）以及通过细胞因子释放来促进免疫反应。一般来说，肿瘤细胞往往无法展现出这些免疫刺激特性中的任何一种。基于树突状细胞的疫苗越来越受欢迎，因为这些细胞能够将TAA正确地呈递给免疫系统，从而规避肿瘤细胞较差的抗原呈递能力。树突状细胞可以通过其天然的内吞能力，或者通过基因改造来“负载”TAA或其他分子。
