University of California Los Angeles (UCLA), CA, USA.
J Transl Med. 2010 Sep 27;8:89. doi: 10.1186/1479-5876-8-89.
Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.
The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity.
Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by in vitro immune monitoring assays.
The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.
NCT00107159.
几项单中心研究已经提供了证据，证明用树突状细胞（DC）进行治疗性疫苗接种可在转移性黑色素瘤患者中引起免疫激活和抗肿瘤活性。在一项具有集中 DC 制造的多中心两阶段 2 期研究中，测试了这种方法在预后良好的转移性黑色素瘤患者中的疗效，这些患者的转移仅限于皮肤、皮下组织和肺（IIIc 期、M1a、M1b）。
该疫苗（IDD-3）由 8 剂源自自体单核细胞的成熟 DC 组成，这些 DC 是在无血清培养基中用粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素 13（IL-13）生成的，用三种同种异体黑色素瘤细胞系的裂解物脉冲处理，并成熟化用干扰素 γ。主要终点是抗肿瘤活性。
在接受 IDD-3 治疗的 33 名患者中，有 1 名完全缓解（CR），2 名部分缓解（PR），6 名患者的疾病稳定（SD）持续超过 8 周。总体上前瞻性定义的肿瘤生长控制率为 27%（90%置信区间为 13-46%）。IDD-3 给药的毒性极小，并且通过体外免疫监测测定，它导致了对免疫黑色素瘤抗原的高频率免疫激活。
负载肿瘤裂解物的成熟 DC 的给药在有限的转移性黑色素瘤患者中具有显著的免疫原性和抗肿瘤活性。
NCT00107159。
