Foon K A, Oseroff A R, Vaickus L, Greenberg S J, Russell D, Bernstein Z, Pincus S, Köhler H, Seon B K, Tahaoglu E
Lucille Parker Markey Cancer Center, Department of Medicine, Lexington, Kentucky 40536-0093, USA.
Clin Cancer Res. 1995 Nov;1(11):1285-94.
We generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) to a highly restricted T-cell antigen designated glycoprotein (gp) 37 that is found on T-cell malignancies but not on normal cells. gp37 is identified by the murine monoclonal antibody SN2 (Ab1) against which the Ab2 was raised. Each of four patients with T-cell lymphoma predominantly confined to the skin received a minimum of four intracutaneous injections of aluminum hydroxide precipitated anti-idiotype murine monoclonal antibody (1 mg/injection) given every 2 weeks. For responding patients, injections were continued on a monthly basis. All tumors were measured along orthogonal major and minor axes, using a ruler and/or calipers, by the same observer. Tumor sizes were documented photographically. Three of the four patients developed specific idiotypic humoral immune responses, and two of the four patients also demonstrated idiotypic cell-mediated responses. Humoral responses included binding of the patients' sera to the anti-idiotype antibody as well as specific inhibition of binding of the SN2 antibody (Ab1) to the anti-idiotype antibody (Ab2). Anti-anti-idiotypic (Ab3) antibody from one patient's serum bound specifically to the gp37-positive cell line MOLT-4 and also to semipurified gp37 antigen. Cell-mediated responses were demonstrated by specific proliferative response to the aluminum hydroxide precipitated anti-idiotype antibody by patients' peripheral blood mononuclear cells. While three of the four patients had extensive disease and did not have clinical responses, one of the patients who had nine discrete skin tumors and peripheral blood involvement without other detectable disease had virtually complete disappearance of the tumors lasting over 11 months. Our results demonstrate that this particular anti-idiotype antibody can induce humoral and cellular immune responses, and at least in one patient led to a meaningful therapeutic response. Future trials should focus on immunocompetent patients with minimal disease.
我们制备了一种IgG1小鼠单克隆抗独特型抗体（Ab2），针对一种高度限制性的T细胞抗原，即糖蛋白（gp）37，该抗原存在于T细胞恶性肿瘤细胞上，而正常细胞上没有。gp37由小鼠单克隆抗体SN2（Ab1）识别，Ab2就是针对该抗体产生的。四名主要局限于皮肤的T细胞淋巴瘤患者每人至少接受了四次皮内注射氢氧化铝沉淀的抗独特型小鼠单克隆抗体（每次注射1毫克），每两周注射一次。对于有反应的患者，每月继续注射。所有肿瘤均由同一名观察者使用尺子和/或卡尺沿正交的长轴和短轴进行测量。肿瘤大小通过拍照记录。四名患者中有三名产生了特异性独特型体液免疫反应，四名患者中有两名还表现出独特型细胞介导的反应。体液反应包括患者血清与抗独特型抗体的结合，以及对SN2抗体（Ab1）与抗独特型抗体（Ab2）结合的特异性抑制。一名患者血清中的抗抗独特型（Ab3）抗体特异性结合gp37阳性细胞系MOLT-4以及半纯化的gp37抗原。患者外周血单核细胞对氢氧化铝沉淀的抗独特型抗体产生特异性增殖反应，证明了细胞介导的反应。虽然四名患者中有三名病情广泛且无临床反应，但其中一名患者有九个离散的皮肤肿瘤且外周血受累，无其他可检测到的疾病，其肿瘤几乎完全消失，持续了11个月以上。我们的结果表明，这种特定的抗独特型抗体可以诱导体液和细胞免疫反应，至少在一名患者中产生了有意义的治疗反应。未来的试验应侧重于疾病轻微的免疫功能正常的患者。
