Miller G A, Pontes J E, Huben R P, Goldrosen M H
Cancer Res. 1985 Sep;45(9):4478-82.
The object of this study was to characterize the antigens evoking an immune response in renal cell carcinoma (RCC) patients receiving specific active immunotherapy with irradiated autologous tumor cells and Corynebacterium parvum as adjuvant. Seventy serum samples from 11 patients with RCC undergoing specific active immunotherapy were evaluated. Fifty of the 70 serum specimens (71%) had immunoglobulin G antibody directed to autologous tumor cells. Absorption studies were completed on 4 patients (S.E., M.M., R.N., S.V.) with 2 patients (S.V. and M.M.) demonstrating reactivity to a RCC-associated antigen present on their autologous tumor cells. One patient's serum (R.N.) was absorbed not only with autologous tumor cells but also with an allogeneic RCC cell line. The fourth patient's (S. E.) serum reactivity was able to be absorbed only with autologous tumor cells and several, but not all, of the clones of that autologous cell line. Patient S.E. serum binding by clones of RCC cell line RPMI-SE was seen to vary from no ability to bind RPMI-SE in some clones to double the parental binding in others. Consistent with this finding was the demonstration that high serum-binding clones could absorb Patient S.E. serum reactivity to autologous RCC cells, while low binding clones could not. These data suggest a measure of heterogeneity among the parental RCC cell line, as demonstrated by its clones. This study has shown that the autologous tumor vaccine with adjuvant used here was an immunogenic therapeutic agent. The response mounted by these patients was a response to a RCC-associated antigen with the level of reactivity changing with the number of immunizations and disease status. Also suggested by this work is the possible primary tumor heterogeneity, as demonstrated by the differential reactivity seen among clones of a RCC cell line established from such a primary tumor.
本研究的目的是鉴定在接受以辐照自体肿瘤细胞和短小棒状杆菌作为佐剂的特异性主动免疫治疗的肾细胞癌（RCC）患者中引发免疫反应的抗原。对11例接受特异性主动免疫治疗的RCC患者的70份血清样本进行了评估。70份血清标本中有50份（71%）含有针对自体肿瘤细胞的免疫球蛋白G抗体。对4例患者（S.E.、M.M.、R.N.、S.V.）进行了吸收研究，其中2例患者（S.V.和M.M.）显示对其自体肿瘤细胞上存在的RCC相关抗原具有反应性。1例患者（R.N.）的血清不仅被自体肿瘤细胞吸收，还被一种同种异体RCC细胞系吸收。第4例患者（S.E.）的血清反应性仅能被自体肿瘤细胞以及该自体细胞系的几个（但不是全部）克隆吸收。观察到RCC细胞系RPMI-SE的克隆对患者S.E.血清的结合能力各不相同，一些克隆无法结合RPMI-SE，而另一些克隆的结合能力是亲本结合能力的两倍。与此发现一致的是，高血清结合克隆能够吸收患者S.E.血清对自体RCC细胞的反应性，而低结合克隆则不能。这些数据表明亲本RCC细胞系之间存在一定程度的异质性，其克隆也证明了这一点。本研究表明，这里使用的带有佐剂的自体肿瘤疫苗是一种免疫原性治疗剂。这些患者产生的反应是对RCC相关抗原的反应，反应性水平随免疫次数和疾病状态而变化。这项研究还表明，可能存在原发性肿瘤异质性，从由这种原发性肿瘤建立的RCC细胞系的克隆之间观察到的不同反应性可以看出。
