TREATMENT OF METASTATIC MELANOMA WITH AN AUTOLOGOUS TUMOR-CELL VACCINE - CLINICAL AND IMMUNOLOGICAL RESULTS IN 64 PATIENTS
TREATMENT OF METASTATIC MELANOMA WITH AN AUTOLOGOUS TUMOR-CELL VACCINE - CLINICAL AND IMMUNOLOGICAL RESULTS IN 64 PATIENTS
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DOI：
10.1200/jco.1990.8.11.1858
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发表时间：
1990-11-01
影响因子：
45.3
通讯作者：
MASTRANGELO, MJ
中科院分区：
文献类型：
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作者：
BERD, D;MAGUIRE, HC;MASTRANGELO, MJ
我们治疗了64例转移性黑色素瘤患者，在使用黑色素瘤疫苗之前使用低剂量环磷酰胺（CY），并监测免疫效果和抗肿瘤活性。第0天给予环磷酰胺300 mg/m2静脉滴注。三天后，用由10至25 × 10 - 10组成的疫苗皮内注射。106个自体的、酶促解离的、冷冻保存的、与卡介苗（BCG）混合的辐射（25戈伊）肿瘤细胞。每28天重复一次该治疗序列。在40例可评估的可测量转移患者中，5例有缓解，4例完全缓解，1例部分缓解，中位持续时间为10个月（7至84 +个月）。在另外6名患者中，我们观察到了这种疫苗疗法特有的抗肿瘤反应：免疫治疗开始后出现的转移性病变消退。免疫治疗后，对未暴露于外源性抗原（如酶或胎牛血清）的自体、机械分离的黑素瘤细胞的迟发型超敏反应（DTH）显著增加（第0天对第49天，P <0.001;第0天对第161天，P <0.001;第0天对第217天，P = 0.021）。对疫苗的抗肿瘤应答与DTH密切相关，如以下三项观察结果所示：（1）10例肿瘤消退患者中有8例DTH阳性，（2）术后辅助治疗患者中，DTH阳性与肿瘤消退呈高度显著的线性关系，自体黑色素瘤细胞的DTH强度与肿瘤复发时间之间有显著性差异（P <0.001），（3）9名在其原始疫苗中对自体黑素瘤细胞产生DTH的患者产生了新的转移，这些转移未能引起DTH或引起小得多的反应。在三个病例中，我们能够切除退化的肿瘤进行组织学检查，这些肿瘤的特点是强烈的淋巴细胞浸润。这一证据表明，黑色素瘤相关抗原的免疫反应，可以引起癌症患者提供了一些乐观的发展前景，主动免疫疗法，具有实际的治疗价值的基础。
We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 .times. 106 autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guerin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84 + months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P < .001; day 0 v day 161, P < .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P < .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value.