Roehnisch Tim, Then Cornelia, Nagel Wolfgang, Blumenthal Christina, Braciak Todd, Donzeau Mariel, Böhm Thomas, Bourquin Carole, Oduncu Fuat
Division of Hematology and Oncology, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, D-80336, Munich, Germany.
J Transl Med. 2013 Oct 23;11:267. doi: 10.1186/1479-5876-11-267.
B cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine.
In the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed.
Feasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2±23.8 days vs. 41.8±1.6 days and 39.8±3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype.
We present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies.
B细胞恶性肿瘤的特征是B细胞克隆性扩增，其表面表达肿瘤特异性独特型。这些独特型是个体化免疫治疗的理想靶抗原。然而，由于独特型免疫原性低，以往的独特型疫苗大多缺乏有效性。本研究的目的是确定一种新型化学连接的噬菌体独特型疫苗的可行性、安全性和免疫原性。
在小鼠B细胞淋巴瘤1模型中，将肿瘤独特型化学连接到用作免疫载体的噬菌体颗粒上。作为对照，将独特型基因表达在主要噬菌体外壳蛋白g8上或与钥孔戚血蓝蛋白连接。用独特型疫苗进行皮内免疫后，评估耐受性和体液免疫反应。
证明了化学连接的噬菌体独特型疫苗的可行性和耐受性。用表达B细胞淋巴瘤1独特型的噬菌体进行疫苗接种，在小鼠B细胞淋巴瘤1保护模型中产生了显著的生存获益（接种野生型噬菌体或磷酸盐缓冲盐水后分别为41.8±1.6天和39.8±3.8天，接种表达B细胞淋巴瘤1独特型的噬菌体后为60.2±23.8天）。与基因工程噬菌体独特型和钥孔戚血蓝蛋白偶联的独特型疫苗相比，化学连接的噬菌体独特型疫苗具有更高的免疫原性，这通过接种化学连接的噬菌体独特型后显著更高的B细胞淋巴瘤1独特型特异性IgG水平得以证明。
我们提出了一种新型、简单、省时且经济高效的噬菌体独特型疫苗接种策略，该策略代表了一种安全可行的治疗方法，与先前采用的独特型疫苗接种策略相比，可能产生更好的免疫反应。
