Novel immunotherapy for Hematological Malignancy

我们已经分离出白血病特异性融合基因，CEV14-PDGFRβ和TEL-Syk，以及突变FLT3受体。用SEREX方法从白血病基因中分离出16个基因。这些基因产物具有免疫原基序和抗体应答。DNA疫苗接种已成为一种有吸引力的肿瘤免疫治疗方法。利用Herios基因枪（Bio-Rad）轰击含DNA的金颗粒技术，可以在体外和体内将基因转移到多种组织中。本研究的目的是评价基因在体外转移的效率和DNA疫苗在预防和治疗小鼠恶性肿瘤中的效力。采用基因枪法在C3H/He J小鼠体内皮下接种含有突变FLT3R表达载体或半乳糖苷酶表达载体的DNA疫苗。免疫后，用转染突变FLT3R表达载体的1.5×10^7肿瘤32D细胞腹腔内刺激小鼠。在肿瘤预防和肿瘤消退实验中分析抗肿瘤免疫。用突变型FLT3R表达载体免疫小鼠后，小鼠可预防肿瘤，并对肿瘤细胞产生抗体。用半乳糖苷酶表达载体免疫小鼠，肿瘤侵袭后14天内可触及肿块，但肿块消失。对照小鼠出现可触及且逐渐生长的肿瘤。

We have isolated leukemia specific fusion genes, CEV14-PDGFRβ and TEL-Syk, and mutant FLT3 Receptor. Also sixteen genes were isolated from leukemia genes using SEREX methods. These gene products have immnogenic motif and antibody response.DNA vaccination has emerged as an attractive approach for tumor immunotherapy. The technique of gold particle containing DNA bombardment by Herios Gene Gun (Bio-Rad) can be used to transfer genes to several tissues in vitro and in vivo. The aim of this study was to evaluate the efficiency of gene transfer in vitro and the potency of DNA vaccines in preventing and treating murine malignant tumor. We used the gene gun method to vaccinate C3H/He J mice intradermally with DNA vaccines containing the mutant FLT3R expression vector or the galactosidase expression vector in vivo. After immunization, mice were challenged intracutaneously on the abdomen with 1.5×10^7 tumorous 32D cells which transfected mutant FLT3R expression vector. Antitumor immunity was analyzed in both tumor prevention and tumor regression experiments. Mice immunized with mutant FLT3R expression vector prevented tumor and had antibody for tumor cells. In mice immunized with the galactosidase expression vector, tumor masses were palpable within 14 days after tumor challenge but disappeared. Control mice developed palpable and progressively growing tumors.