Galligioni E, Quaia M, Merlo A, Carbone A, Spada A, Favaro D, Santarosa M, Sacco C, Talamini R
Centro di Riferimento Oncologico, Aviano, Italy.Gruppo Oncologico Clinico Cooperativo del Nord-Est.
Cancer. 1996 Jun 15;77(12):2560-6. doi: 10.1002/(SICI)1097-0142(19960615)77:12<2560::AID-CNCR20>3.0.CO;2-P.
Active specific immunotherapy (ASI) is a strategy that attempts to boost the host's immune response specifically against its own tumor. The purpose of this study was to investigate the effect of adjuvant ASI in patients with renal carcinoma.
Of 120 consecutive patients, 60 were randomized to a control group and 60 to receive ASI comprised of 3 intradermal injections of 10(7) autologous irradiated tumor cells mixed with 10(7) Bacillus Calmette-Guèrin (in the first 2 vaccinations) or alone. At randomization and 1, 6, and 12 months after completing immunotherapy, the treated patients were evaluated for the development of delayed type cutaneous hypersensitivity (DTCH) response to autologous tumor and autologous normal renal cells.
The baseline DTCH responses were negative in all patients. One month after completing ASI, 38 of 54 immunized patients showed a significant (P<0.01) DTCH response to autologous tumor but not to autologous normal renal cells. The response was persistent at 6 months in 25 of 44 patients and at 12 months in 16 of 28 patients. DTCH response remained negative in the nonimmunized control patients. There was no systemic toxicity but local ulcerations that healed in 2 months were observed. After a median follow-up of 61 months, the probability of 5-year disease free survival (DFS) was 63% for treated patients and 72% for control patients. The corresponding probability of 5-year overall survival (OS) was 69% and 78%, respectively. These differences were not statistically significant.
This is the first prospective randomized study of ASI in a large population of patients with renal carcinoma after radical nephrectomy. Our data clearly indicate that ASI can increase the reactivity to autologous tumor, as measured by the DTCH test, but it appears unable to affect DFS and OS of patients.
主动特异性免疫疗法（ASI）是一种试图增强宿主针对自身肿瘤的特异性免疫反应的策略。本研究的目的是调查辅助性ASI对肾癌患者的影响。
在120例连续患者中，60例被随机分配到对照组，60例接受由3次皮内注射10⁷个自体照射肿瘤细胞与10⁷个卡介苗（在前2次接种中）混合或单独使用组成的ASI。在随机分组时以及完成免疫治疗后的1、6和12个月，对接受治疗的患者进行评估，以确定其对自体肿瘤和自体正常肾细胞的迟发型皮肤超敏反应（DTCH）。
所有患者的基线DTCH反应均为阴性。完成ASI治疗1个月后，54例免疫患者中有38例对自体肿瘤表现出显著（P<0.01）的DTCH反应，但对自体正常肾细胞无反应。44例患者中有25例在6个月时反应持续存在，28例患者中有16例在12个月时反应持续存在。未免疫的对照患者的DTCH反应仍为阴性。未观察到全身毒性，但观察到局部溃疡，2个月内愈合。中位随访61个月后，治疗患者的5年无病生存率（DFS）概率为63%，对照患者为72%。相应的5年总生存率（OS）概率分别为69%和78%。这些差异无统计学意义。
这是首次对大量根治性肾切除术后肾癌患者进行的ASI前瞻性随机研究。我们的数据清楚地表明，通过DTCH试验测量，ASI可增加对自体肿瘤的反应性，但似乎无法影响患者的DFS和OS。
