Mitchell M S, Harel W, Kempf R A, Hu E, Kan-Mitchell J, Boswell W D, Dean G, Stevenson L
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
J Clin Oncol. 1990 May;8(5):856-69. doi: 10.1200/JCO.1990.8.5.856.
Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.
25例转移性黑色素瘤患者接受了一种治疗性疫苗（“theraccine”）治疗，该疫苗由同种异体黑色素瘤裂解物和一种新型佐剂DETOX（Ribi免疫化学研究公司，蒙大拿州汉密尔顿）组成。每位患者在第1、2、3、4和6周皮下注射200个抗原单位（20×10⁶个肿瘤细胞等效物）。临床反应包括1例完全缓解、3例部分缓解和1例长期（17个月）病情稳定。另外2例患者有混合反应，多个皮下结节部分缓解。有反应的疾病部位主要包括皮肤，但回肠、乳腺和一处肝转移灶也有反应。对部分缓解患者残留病灶进行切除，这些患者的其他病灶在治疗期间已消失，从而实现了长期无病生存。缓解的中位持续时间为17个月，5例有反应的患者中有4例在治疗后存活至少24个月。当考虑完全缓解、部分缓解、混合反应和长期稳定情况时，细胞毒性T细胞（CTL）前体的增加与临床结果相关。CTL可识别许多细胞系上的黑色素瘤相关抗原，但不能识别其他类型的肿瘤或正常淋巴细胞。对黑色素瘤抗原的皮肤试验反应性和针对黑色素瘤细胞的血清抗体与临床反应无关。毒性极小，主要局限于注射部位的轻微疼痛。只有5例患者出现严重肉芽肿，其中4例接受了重复疗程治疗。这些结果证实，用佐剂DETOX给予同种异体黑色素瘤裂解物进行主动特异性免疫可诱导对黑色素瘤的免疫，并可使一部分转移性疾病患者的病情出现缓解，且毒性很小。
