Lotem M, Shiloni E, Pappo I, Drize O, Hamburger T, Weitzen R, Isacson R, Kaduri L, Merims S, Frankenburg S, Peretz T
Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem 91120, Israel.
Br J Cancer. 2004 Feb 23;90(4):773-80. doi: 10.1038/sj.bjc.6601563.
This paper is a report of response rate (RR) and survival of 34 metastatic melanoma patients who received a dinitrophenyl (DNP)-modified autologous melanoma cell vaccine. In all, 27 patients started the vaccine as a primary treatment for metastatic melanoma and seven started it as an adjuvant, with no evidence of disease at the time, but had developed new metastases. Interleukin-2 (IL-2) was administered in 24 out of the 34 patients: 19 who progressed on vaccine alone and five who had the combination from start. Interleukin-2 was administered in the intravenous, bolus high-dose regimen (seven patients) or as subcutaneous (s.c.) low-dose treatment (17). Overall response for the entire group was 35% (12 patients out of 34), 12% having a complete response (CR) and 23% a partial response (PR). However, only two patients had tumour responses while on the vaccine alone, whereas the other 10 demonstrated objective tumour regression following the combination with IL-2 (two CR, eight PR), lasting for a median duration of 6 months (range 3-50 months). Of the 12 responding patients, 11 attained strong skin reactivity to the s.c. injection of irradiated, unmodified autologous melanoma cells. None of the patients with a negative reactivity experienced any tumour response. Patients with positive skin reactions survived longer (median survival - 54 months). The results suggest enhanced RRs to the combination of IL-2 and autologous melanoma vaccine. Skin reactivity to unmodified autologous melanoma cells may be a predictor of response and improved survival, and therefore a criterion for further pursuing of immunotherapeutic strategies.
本文报告了34例接受二硝基苯基（DNP）修饰的自体黑色素瘤细胞疫苗治疗的转移性黑色素瘤患者的缓解率（RR）和生存率。共有27例患者开始使用该疫苗作为转移性黑色素瘤的主要治疗方法，7例作为辅助治疗开始使用，当时无疾病证据，但已出现新的转移灶。34例患者中有24例接受了白细胞介素-2（IL-2）治疗：19例仅接受疫苗治疗病情进展，5例从一开始就接受联合治疗。白细胞介素-2采用静脉推注高剂量方案（7例患者）或皮下（s.c.）低剂量治疗（17例）。整个组的总体缓解率为35%（34例患者中有12例），12%为完全缓解（CR），23%为部分缓解（PR）。然而，仅1例患者在仅接受疫苗治疗时出现肿瘤反应，而其他10例在与IL-2联合治疗后出现客观肿瘤消退（2例CR，8例PR），持续时间中位数为6个月（范围3 - 50个月）。在12例有反应的患者中，11例对皮下注射经辐照的、未修饰的自体黑色素瘤细胞表现出强烈的皮肤反应性。皮肤反应性为阴性的患者均未出现任何肿瘤反应。皮肤反应性为阳性的患者生存期更长（中位生存期 - 54个月）。结果表明，IL-2与自体黑色素瘤疫苗联合使用可提高缓解率。对未修饰的自体黑色素瘤细胞的皮肤反应性可能是反应和生存期改善的预测指标，因此是进一步推行免疫治疗策略的一个标准。
