Therapeutic use of immunomodulators and ionizining radiation

我们已获得开始该项目所需的所有必要动物方案许可和试剂。使用的细胞系是高免疫原性黑色素瘤和肾细胞癌细胞系。此外，免疫原性较低的肺癌细胞系被用作比较。在初步实验中，我们已经确定了植入所需的细胞数量，以便产生用于治疗的肿瘤。我们还确定了控制实验的最佳辐射剂量。在正在进行的实验中，我们正在改变抗PD1和抗CTLA4抗体相对于辐射的给药时间，以确定是否对肿瘤反应有任何影响。此外，我们已经获得了以与上述类似的方式用辐射测试Toll样受体7和8激动剂的动物方案。Toll样受体（TLR）识别与病原体相关的分子模式。在识别这些模式后，TLR向先天免疫系统发出信号以增加监视和攻击。

We have obtained all necessary animal protocol permissions and reagents necessary to begin this project. The cell lines being used are the highly immunogenic melanoma and renal cell carcinoma cell lines. In addition, lung cancer cell lines, which are less immunogenic are being used as a comparison. In preliminary experiments, we have determined the number of cells necessary for implant in order to generate tumors for treatment. We have also determined the optimal dose of radiation for control experiments. In ongoing experiments, we are varying the time of administration of anti-PD1 and anti-CTLA4 antibodies relative to radiation to determine if there is any effect on tumor response. In addition, we have obtained an animal protocol to test Toll-like receptor 7 and 8 agonists with radiation in a similar manner to that described above. Toll-like receptors (TLRs) recognize molecular patterns associated with pathogens. After recognition of these patterns, TLRs signal the innate immune system to increase surveillance and attack.