Department of Medical Oncology,Nijmegen Centre for Molecular Life Sciences, and Laboratory of Medical Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Clin Cancer Res. 2011 Sep 1;17(17):5725-35. doi: 10.1158/1078-0432.CCR-11-1261. Epub 2011 Jul 19.
It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine.
HLA-A2.1(+) melanoma patients scheduled for regional lymph node dissection were vaccinated four times biweekly via intradermal or intranodal injection with 12 × 10⁶ to 17 × 10⁶ mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH). Half of the patients also received low-dose IL-2 (9 MIU daily for 7 days starting 3 days after each vaccination). KLH-specific B- and T-cell responses were monitored in blood. gp100- and tyrosinase-specific T-cell responses were monitored in blood by tetramer analysis and in biopsies from delayed-type hypersensitivity (DTH) skin tests by tetramer and functional analyses with (51)Cr release assays or IFNγ release, following coculture with peptide-pulsed T2 cells or gp100- or tyrosinase-expressing tumor cells.
In 19 of 43 vaccinated patients, functional tumor antigen-specific T cells could be detected. Although significantly more DCs migrated to adjacent lymph nodes upon intranodal vaccination, this was also highly variable with a complete absence of migration in 7 of 24 intranodally vaccinated patients. Intradermal vaccinations proved superior in inducing functional tumor antigen-specific T cells. Coadministration of IL-2 did not further augment the antigen-specific T-cell response but did result in higher regulatory T-cell frequencies.
Intradermal vaccination resulted in superior antitumor T-cell induction when compared with intranodal vaccination. No advantage of additional IL-2 treatment could be shown.
目前尚不清楚给药途径是否会影响树突状细胞（DC）为基础的免疫治疗。我们比较了皮内和皮内注射 DC 疫苗对黑素瘤患者诱导免疫反应的效果，并研究了同时给予白细胞介素（IL）-2 是否会增加 DC 疫苗的疗效。
计划进行区域淋巴结清扫的 HLA-A2.1(+)黑素瘤患者通过皮内或皮内注射，每两周接受一次 12×10⁶ 至 17×10⁶ 负载酪氨酸酶和 gp100 肽以及钥孔血蓝蛋白（KLH）的成熟 DC 疫苗，共进行四次。一半患者还接受低剂量 IL-2（9 MIU 每日，在每次接种后第 3 天开始连续 7 天）治疗。在血液中监测 KLH 特异性 B 细胞和 T 细胞反应。通过四聚体分析监测血液中的 gp100 和酪氨酸酶特异性 T 细胞反应，并通过延迟型超敏反应（DTH）皮肤试验活检中的四聚体和功能分析（用 51Cr 释放测定或 IFNγ 释放）监测，方法是用肽脉冲 T2 细胞或 gp100 或酪氨酸酶表达肿瘤细胞进行共培养。
在 43 名接种疫苗的患者中，有 19 名检测到功能性肿瘤抗原特异性 T 细胞。虽然皮内接种疫苗时明显有更多的 DC 迁移到相邻淋巴结，但在 24 名皮内接种疫苗的患者中，有 7 名完全没有迁移，这种情况也高度可变。皮内接种疫苗在诱导功能性肿瘤抗原特异性 T 细胞方面效果更好。同时给予 IL-2 并不能进一步增强抗原特异性 T 细胞反应，但确实导致调节性 T 细胞频率升高。
与皮内接种疫苗相比，皮内接种疫苗可诱导更好的抗肿瘤 T 细胞。同时给予 IL-2 治疗没有显示出优势。
