Phase I/II study of treatment with matured dendritic cells with or without low dose IL-2 in patients with disseminated melanoma
Phase I/II study of treatment with matured dendritic cells with or without low dose IL-2 in patients with disseminated melanoma
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DOI：
10.1007/s00262-007-0435-8
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发表时间：
2008-07-01
影响因子：
5.8
通讯作者：
Menzies, S. W.
中科院分区：
文献类型：
--
作者：
Hersey, P.;Halliday, G. M.;Menzies, S. W.
背景在本研究中，我们研究了成熟的树突状细胞(DC)疫苗加或不加小剂量IL-2对转移性黑色素瘤患者的治疗效果。方法16例患者接受了自体黑色素瘤裂解物致敏的DC疫苗，18例患者接受了gp100、MART-1、酪氨酸酶、MAGE-3.A2、MAGE-A10和NA17多肽致敏的DC。每组各一半于每次注射后第2天皮下注射IL-2，剂量为1MU/m(2)，疗程5~14d。结果接受DC+多肽+IL-2治疗的9例患者，部分缓解(PR)2例，病情稳定(SD)3例；接受DC+多肽+IL-2治疗的9例，PR和SD各1例。在接受DC+自体裂解物而不接受IL-2的组中，只有两名SD患者。所有患者的中位总存活率在18.5个月时非常好，但这最可能是因为为研究选择了一组有利的患者。经对数等级分析，两组间的生存率差异无统计学意义。治疗与显著的副作用无关。结论成熟DC制剂对黑色素瘤多肽的呈递能力可能优于未成熟DC制剂，IL-2可提高DC联合多肽的临床疗效。然而，在我们看来，低应答率并不能证明这种治疗方法的成本和复杂性是合理的。
Background In the present study, we have examined whether treatment of patients with metastatic melanoma with matured dendritic cell (DC) vaccines with or without low dose IL-2 may improve treatment outcomes.Methods Sixteen patients received DC vaccines (DCs) sensitized with autologous melanoma lysates and 18 patients received DCs sensitized with peptides from gp100, MART-1, tyrosinase, MAGE-3.A2, MAGE-A10 and NA17. IL-2 was given subcutaneously (sc) at 1 MU/m(2) on the second day after each injection for 5-14 days in half of each group. DCs were given by intranodal injection.Results There were 2 partial responses (PR) and 3 with stable disease (SD) in the nine patients receiving DCs + peptides + IL-2, and 1 PR and 1 SD in nine patients treated with DCs + peptides without IL-2. There were only two patients with SD in the group receiving DCs + autologous lysates and no IL-2. Median overall survival for all patients was very good at 18.5 months but this was most probably due to selection of a favourable group of patients for the study. There was no significant difference in survival between the groups by log rank analysis. Treatment was not associated with significant side effects. The quality and yield of the DCs in the preparations were generally good.Conclusions We conclude that mature DC preparations may be superior to immature DC preparations for presentation of melanoma peptides and that IL-2 may increase clinical responses to the DCs plus peptides. However, in our view the low response rates do not justify the cost and complexity of this treatment approach.