Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine
Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine
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DOI：
10.1200/jco.2004.06.043
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发表时间：
2004-02-01
影响因子：
45.3
通讯作者：
Mastrangelo, MJ
中科院分区：
文献类型：
--
作者：
Berd, D;Sato, T;Mastrangelo, MJ
目的 我们之前报道了一项人类癌症疫苗的临床试验，该疫苗由经过半抗原二硝基苯基 (DNP) 修饰的自体肿瘤细胞组成，用于临床 III 期黑色素瘤患者。在这里，我们提出了一份扩大到 214 名患者的随访报告，随访时间为 5 年。 患者和方法 对 214 名临床 III 期黑色素瘤患者（117 名 IIIC 期患者和 97 名 IIIB 期患者）进行标准淋巴结切除术后无黑色素瘤，接受多次皮内注射自体 DNP 改良疫苗与卡介苗混合的治疗。依次测试了四种疫苗剂量方案，所有这些都包括低剂量环磷酰胺。测试患者对自体黑色素瘤细胞（DNP 修饰和未修饰）以及对照材料的迟发型超敏反应 (DTH)。结果 214 名患者的 5 年总生存 (OS) 率为 44%。 47% 的患者诱导了对未经修饰的自体黑色素瘤的 DTH 反应。该 DTH 阳性组的 OS 是 DTH 阴性患者的两倍 (59.3% vs 29.3%；P < .001)。相比之下，几乎所有患者都对 DNP 修饰的自体黑色素瘤细胞和纯化蛋白衍生物产生阳性 DTH 反应，但不影响 OS。令人惊讶的是，未修饰肿瘤细胞 DTH 呈阳性的患者复发后的 OS 也显着更长 (25.2% vs 12.3%；P < .001)。最后，DTH 的发展取决于疫苗的给药时间表，特别是在治疗计划开始时给予诱导剂量的时间。 结论 这项研究强调了自体 DNP 修饰疫苗的免疫药理学的重要性，并且可能与其他癌症疫苗技术相关。 (C) 2004 年，美国临床肿瘤学会。
Purpose We have previously reported a clinical trial of a human cancer vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients with clinical stage III melanoma. Here we present a follow-up report expanded to 214 patients with 5-year follow-up.Patients and Methods Two hundred fourteen patients with clinical stage III melanoma (117 patients with stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard lymphadenectomy were treated with multiple intradermal injections of autologous, DNP-modified vaccine mixed with bacille Calmette-Guerin. Four vaccine dosage schedules were tested sequentially, all of which included low-dose cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to autologous melanoma cells, both DNP-modified and unmodified, and to control materials.Results The 5-year overall survival (OS) rate of the 214 patients was 44%. DTH responses to unmodified autologous melanoma were induced in 47% of patients. The OS of this DTH-positive group was double that of DTH-negative patients (59.3% v 29.3%; P < .001). In contrast, positive DTH responses to DNP-modified autologous melanoma cells and to purified protein derivative developed in almost all patients but did not affect OS. Surprisingly, the OS after relapse was also significantly longer in patients who developed positive DTH to unmodified tumor cells (25.2% v 12.3%; P < .001). Finally, the development of DTH was dependent on the schedule of administration of the vaccine, specifically, the timing of an induction dose administered at the beginning of the treatment program.Conclusion This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies. (C) 2004 by American Society of Clinical Oncology.