Institute of Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Immunol Rev. 2010 May;235(1):159-71. doi: 10.1111/j.0105-2896.2010.00894.x.
Granzyme B (GzmB) is used by cytotoxic lymphocytes as a molecular weapon for the defense against virus-infected and malignantly transformed host cells. It belongs to a family of small serine proteases that are stored in secretory vesicles of killer cells. After secretion of these cytolytic granules during killer cell attack, GzmB is translocated into the cytosol of target cells with the help of the pore-forming protein perforin. GzmB has adopted similar protease specificity as caspase-8, and once delivered, it activates major executioner apoptosis pathways. Since GzmB is very effective in killing human tumor cell lines that are otherwise resistant against many cytotoxic drugs and since GzmB of human origin can be recombinantly expressed, its use as part of a 'magic bullet' in tumor therapy is a very tempting idea. In this review, we emphasize the peculiar characteristics of GzmB that make it suited for use as an effector domain in potential immunoconjugates. We discuss what is known about its uptake into target cells and the trials performed with GzmB-armed immunoconjugates, and we assess the prospects of its potential therapeutic value.
颗粒酶 B（GzmB）被细胞毒性淋巴细胞用作抵御病毒感染和恶性转化宿主细胞的分子武器。它属于一类储存在杀伤细胞分泌小泡中的丝氨酸蛋白酶。在杀伤细胞攻击期间这些细胞毒性颗粒分泌后，GzmB 在穿孔蛋白的帮助下易位到靶细胞的细胞质中。GzmB 采用了类似于 caspase-8 的蛋白酶特异性，一旦被递送到靶细胞中，它就会激活主要的执行细胞凋亡途径。由于 GzmB 非常有效地杀死对许多细胞毒性药物具有抗性的人类肿瘤细胞系，并且可以重组表达人类来源的 GzmB，因此将其用作肿瘤治疗中“神奇子弹”的一部分是一个非常诱人的想法。在这篇综述中，我们强调了 GzmB 的独特特性，使其适合用作潜在免疫偶联物中的效应结构域。我们讨论了关于其进入靶细胞的摄取以及用 GzmB 武装的免疫偶联物进行的试验，并评估了其潜在治疗价值的前景。
