Eton O, Kharkevitch D D, Gianan M A, Ross M I, Itoh K, Pride M W, Donawho C, Buzaid A C, Mansfield P F, Lee J E, Legha S S, Plager C, Papadopoulos N E, Bedikian A Y, Benjamin R S, Balch C M
Department of Melanoma/Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Clin Cancer Res. 1998 Mar;4(3):619-27.
Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.
我们的目标是确定在转移性黑色素瘤患者中，使用紫外线B（UVB）照射的（UVR）自体肿瘤（AT）细胞加佐剂DETOX进行主动免疫治疗的临床活性、毒性和免疫效应。入选标准包括在切除5克或更多转移性黑色素瘤后完全康复的非无反应性患者。治疗包括每2周皮内注射10(7)个UVR-AT加0.25毫升DETOX，共6次，然后每月注射一次。在首次、第四次、第七次及后续治疗前，采集外周血单个核细胞（PBMC）进行细胞毒性测定，并进行皮肤试验以确定迟发型超敏反应（DTH）。42例患者接受了治疗，其中18例为辅助治疗，24例有可测量的疾病。在后一组中，有两例在软组织部位和一处骨转移出现持久反应。治疗耐受性良好。35例患者可评估免疫参数；其中10例患者，包括2例反应者，表现出PBMC对AT细胞细胞毒性的早期诱导，在治疗期间持续长达10个月，然后降至背景水平。在7例患者中的5例中，这种下降预示着疾病进展。8例患者观察到对AT细胞的迟发型微弱DTH反应的晚期诱导。UVR-AT + DETOX主动免疫治疗在晚期黑色素瘤中具有适度但明确的临床活性。PBMC细胞毒性和对AT细胞的DTH反应性的诱导支持了治疗的特异性全身免疫效应，尽管在本研究中前者更紧密地跟随疾病进程。
