Wang Siqing, Hong Sungyoul, Wezeman Michele, Qian Jianfei, Yang Jing, Yi Qing
Department of Lymphoma and Myeloma, Division of Cancer Medicine, and the Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer, Houston, Texas 77030, USA.
Front Biosci. 2007 May 1;12:3566-75. doi: 10.2741/2335.
Idiotype protein (Id) secreted by myeloma cells is the best-characterized tumor-specific antigen and is widely used in clinical trials of immunotherapy in B-cell tumors. In this study, we used a myeloma murine model to compare the efficacy of two commonly used vaccines in human trials, Id-keyhole limpet hemocyanin (KLH) protein versus Id-KLH-pulsed DC vaccines in preventing or treating myeloma and priming tumor-specific immune responses. Although both vaccines were able to protect mice from developing myeloma, only the DC vaccine induced therapeutic immunity in tumor-bearing mice. DC vaccinations not only retarded tumor growth but also eradicated established myeloma in 60% of mice. The therapeutic efficacy of the DC vaccine was associated with increased tumor-specific IFN-g and IL-4 T-cell responses and cytolytic activity of splenic T cells. Moreover, the vaccines induced tumor-specific immune responses that protected surviving mice from tumor rechallenge. Thus, our results demonstrate that Id-based DC vaccine but not Id-KLH protein vaccine can be therapeutic to established myeloma. Further studies are needed to optimize methods of DC-based vaccines to improve the efficacy of clinical trials.
骨髓瘤细胞分泌的独特型蛋白（Id）是特征最明确的肿瘤特异性抗原，广泛应用于B细胞肿瘤免疫治疗的临床试验。在本研究中，我们使用骨髓瘤小鼠模型比较了两种在人体试验中常用疫苗的疗效，即Id-钥孔血蓝蛋白（KLH）蛋白疫苗与Id-KLH脉冲树突状细胞（DC）疫苗在预防或治疗骨髓瘤以及引发肿瘤特异性免疫反应方面的效果。虽然两种疫苗都能保护小鼠不发生骨髓瘤，但只有DC疫苗能在荷瘤小鼠中诱导治疗性免疫。DC疫苗接种不仅延缓了肿瘤生长，还在60%的小鼠中根除了已形成的骨髓瘤。DC疫苗的治疗效果与肿瘤特异性干扰素-γ和白细胞介素-4 T细胞反应增加以及脾T细胞的细胞溶解活性有关。此外，这些疫苗诱导了肿瘤特异性免疫反应，保护存活小鼠免受肿瘤再次攻击。因此，我们的结果表明，基于Id的DC疫苗而非Id-KLH蛋白疫苗对已形成的骨髓瘤具有治疗作用。需要进一步研究优化基于DC的疫苗方法，以提高临床试验的疗效。
