Center for Cancer Immunotherapy (CCIT), Department of Hematology, Herlev Hospital, Herlev, Denmark.
Cytotherapy. 2010 Oct;12(6):721-34. doi: 10.3109/14653241003774045.
Dendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(−) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b.
Of 46 patients who initiated treatment, 10 stopped treatment within 1-4 weeks because of rapid disease progression and deterioration. After 8 weeks, 36 patients were evaluable: no patient had an objective response, 11 patients had stable disease (SD); six had continued SD after 4 months, and three patients had prolonged SD for more than 6 months. The mean overall survival time was 9 months, with a significantly longer survival (18.4 months) of patients who attained SD compared with patients with progressive disease (PD) (5 months). Induction of antigen-specific T-cell responses was analyzed by multidimensional encoding of T cells using HLA-A2 major histocompatibility complex (MHC) multimers. Immune responses against five high-affinity vaccine peptides were detectable in the peripheral blood of six out of 10 analyzed HLA-A2+ patients. There was no observed correlation between the induction of immune responses and disease stabilization. A significant lower blood level of regulatory T cells (CD25(high) CD4 T cells) was demonstrable after six vaccinations in patients with SD compared with PD.
Vaccination was feasible and safe. Treatment-associated SD was observed in 24% of the patients. SD correlated with prolonged survival suggesting a clinical benefit. Differences in the level of regulatory T cells among SD and PD patients could indicate a significant role of these immune suppressive cells.
树突状细胞被认为是最有效的抗原呈递细胞和免疫反应的协调者，因此适合作为疫苗基础。在这里，我们报告了一项临床研究的结果，该研究中，患有已确诊进展性疾病的恶性黑色素瘤（MM）患者接受了自体单核细胞来源的成熟树突状细胞（DC）疫苗接种，这些 DC 被 p53、survivin 和端粒酶衍生肽（HLA-A2+患者）或自体/异体肿瘤裂解物（HLA-A2（-）患者）脉冲处理，同时联合低剂量白细胞介素（IL）-2 和干扰素（IFN）-α2b。
46 名开始治疗的患者中，有 10 名在 1-4 周内因疾病快速进展和恶化而停止治疗。8 周后，36 名患者可评估：无客观反应患者，11 名患者病情稳定（SD）；6 名患者在 4 个月后持续 SD，3 名患者 SD 持续时间超过 6 个月。平均总生存期为 9 个月，与进展性疾病（PD）患者相比，达到 SD 的患者的生存期显著延长（18.4 个月）（5 个月）。使用 HLA-A2 主要组织相容性复合物（MHC）多聚体对 T 细胞进行多维编码分析了抗原特异性 T 细胞反应。在 10 名分析的 HLA-A2+患者中的 6 名患者的外周血中可检测到针对五种高亲和力疫苗肽的免疫反应。免疫反应的诱导与疾病稳定之间没有观察到相关性。在 SD 患者中，与 PD 患者相比，在 6 次接种后可观察到调节性 T 细胞（CD25（高）CD4 T 细胞）的血水平显著降低。
疫苗接种是可行和安全的。在 24%的患者中观察到治疗相关的 SD。SD 与延长的生存相关，表明具有临床获益。SD 和 PD 患者之间调节性 T 细胞水平的差异可能表明这些免疫抑制细胞具有重要作用。
