Boon T, Cerottini J C, Van den Eynde B, van der Bruggen P, Van Pel A
Ludwig Institute for Cancer Research, Brussels, Belgium.
Annu Rev Immunol. 1994;12:337-65. doi: 10.1146/annurev.iy.12.040194.002005.
Transplantation experiments have demonstrated that most mouse tumors express antigens that can constitute targets for rejection responses mediated by syngeneic T lymphocytes. For human tumors, autologous cultures mixing tumor cells and blood lymphocytes or tumor-infiltrating lymphocytes have produced CD8+ and CD4+ cytolytic T cell (CTL) clones that recognize tumor cells specifically. Attempts to identify the target antigens by biochemical fractionation of tumor cells up to now have failed, with the important exception of the identification of underglycosylated mucins present on breast and pancreatic carcinomas. Gene transfection approaches have proved more successful. A gene family named MAGE codes for antigens recognized by autologous CTL on a melanoma tumor. These genes are not expressed in normal tissues except for testis. They are expressed in many tumors of several histological types. Differentiation antigens coded by genes such as tyrosinase are also recognized on human melanoma by autologous CTL. The identification of human tumor rejection antigens opens new possibilities for systematic approaches to the specific immune therapy of cancer.
移植实验表明,大多数小鼠肿瘤表达的抗原可成为同基因T淋巴细胞介导的排斥反应的靶标。对于人类肿瘤,将肿瘤细胞与血液淋巴细胞或肿瘤浸润淋巴细胞混合进行自体培养,已产生了能特异性识别肿瘤细胞的CD8 +和CD4 +细胞毒性T细胞(CTL)克隆。迄今为止,通过对肿瘤细胞进行生化分级分离来鉴定靶抗原的尝试均告失败,但乳腺癌和胰腺癌中存在的低聚糖化粘蛋白的鉴定是一个重要例外。基因转染方法已被证明更为成功。一个名为MAGE的基因家族编码黑色素瘤肿瘤上自体CTL识别的抗原。这些基因除了在睾丸中表达外,在正常组织中不表达。它们在多种组织学类型的许多肿瘤中表达。由酪氨酸酶等基因编码的分化抗原也能被人类黑色素瘤的自体CTL识别。人类肿瘤排斥抗原的鉴定为癌症特异性免疫治疗的系统方法开辟了新的可能性。