Office of Biomedical Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Transl Med. 2011 Oct 20;9:178. doi: 10.1186/1479-5876-9-178.
Ten cancer patients (Six renal cell carcinoma and four breast cancer patients) were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs) and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration.
Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay), NK activity and the cytokine modulation were measured.
Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses.
Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating antigen-specific immune induction along with reduction of inhibitory immunity were correlated with clinical responses in DC vaccine treated patients.
在一项 I/II 期研究中，用自体树突状细胞 (DC) 和白细胞介素-2 (IL-2) 组成的疫苗治疗了 10 例癌症患者 (6 例肾细胞癌和 4 例乳腺癌患者)，以评估 DC 疫苗相关毒性和抗原特异性免疫改变。
癌症患者每 4 周接受两次自体 CD34+造血干细胞衍生的 GM-CSF/IFN-γ 分化的 DC，用自体肿瘤裂解物和 KLH 冲击。每次皮下注射治疗性 DC 后，引入低剂量 (200MIU) IL-2，作为免疫佐剂连续 14 天。为了确定 DC 疫苗诱导的免疫改变，测量 KLH 特异性淋巴细胞增殖、IFN-γ 分泌 T 细胞数量（ELISPOT 测定）、NK 活性和细胞因子调节。
表达 HLA-DR、CD11c、CD83 和 B7.1/B7.2 的培养 DC 产生 IL-12p70。接种后，患者可耐受。在 1 例 RCC 患者中观察到疾病稳定的临床反应。然而，在没有明确临床反应相关性的情况下，在 6 例患者中诱导了 DC 疫苗相关的抗原特异性免疫反应，包括外周血淋巴细胞增殖和 IFN-r 分泌细胞的数量。此外，接种后 6 例患者的 NK 活性明显增强。在 3 例患者中观察到 DC 疫苗相关的 TGF-β 水平降低或 IL-12p70 水平升高和 CD4+CD25+T 细胞下降。然而，只有在疾病稳定的 RCC 患者中，诱导 IFN-γ 分泌 T 细胞的同时减少 CD4+CD25+T 细胞的刺激和抑制免疫改变的组合与临床反应相关。
数据表明，DC 疫苗联合 IL-2 耐受性良好，无严重副作用。DC 疫苗诱导针对引入抗原的特异性免疫。在接受 DC 疫苗治疗的患者中，免疫参数的组合改变，表明抗原特异性免疫诱导，同时减少抑制性免疫与临床反应相关。
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