Mentzer S J, Wilson R E, Burakoff S J, Herrmann S H
Department of Surgery, Brigham and Women's Hospital, Boston, MA.
Arch Surg. 1988 Oct;123(10):1280-5. doi: 10.1001/archsurg.1988.01400340106019.
Cytolytic T lymphocytes (CTLs) are an efficient immune mechanism for the destruction of foreign or pathogenic cells. Attempts to use CTLs in human cancer therapy have focused on the cell-surface molecules that regulate CTL function. An important molecule in CTL function is the CD3 antigen. Biochemical characterization has suggested that the CD3 antigen may function as a "trigger" for T-lymphocyte activation. To investigate this possibility, we used monoclonal antibody (MAb) to the CD3 antigen to trigger activation of long-term CTL lines. The anti-CD3 MAb was able to trigger killing of a variety of human and mouse tumor cell lines; however, not all tumor cells were lysed by the CTL. The susceptibility of the tumor cells to CTL-mediated lysis appeared to correlate with the binding of the anti-CD3 MAb to the tumor cell surface. The requirement for surface binding of the MAb was tested by covalently cross-linking the anti-CD3 MAb to the tumor cell membrane. Membrane-bound anti-CD3 MAb triggered high levels of CTL-mediated tumor cell killing. Similar results were obtained when anti-CD3 MAb was cross-linked to phosphatidylethanolamine and inserted into the cell membrane. These results indicate that the attachment of anti-CD3 MAb to the tumor cell surface provides a powerful new approach to the in vitro activation of human killer T cells and the in vivo treatment of human cancer.
细胞溶解性T淋巴细胞（CTLs）是破坏外来或致病细胞的一种有效免疫机制。在人类癌症治疗中尝试使用CTLs，重点关注调节CTL功能的细胞表面分子。CTL功能中的一个重要分子是CD3抗原。生化特性表明，CD3抗原可能作为T淋巴细胞激活的“触发器”。为了研究这种可能性，我们使用针对CD3抗原的单克隆抗体（MAb）来触发长期CTL系的激活。抗CD3 MAb能够触发多种人类和小鼠肿瘤细胞系的杀伤；然而，并非所有肿瘤细胞都被CTL裂解。肿瘤细胞对CTL介导的裂解的敏感性似乎与抗CD3 MAb与肿瘤细胞表面的结合相关。通过将抗CD3 MAb与肿瘤细胞膜共价交联来测试MAb表面结合的必要性。膜结合的抗CD3 MAb触发了高水平的CTL介导的肿瘤细胞杀伤。当抗CD3 MAb与磷脂酰乙醇胺交联并插入细胞膜时，也获得了类似的结果。这些结果表明，抗CD3 MAb与肿瘤细胞表面的附着为体外激活人类杀伤性T细胞和体内治疗人类癌症提供了一种强大的新方法。
