VACCINATION WITH IRRADIATED TUMOR-CELLS ENGINEERED TO SECRETE MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR STIMULATES POTENT, SPECIFIC, AND LONG-LASTING ANTITUMOR IMMUNITY
VACCINATION WITH IRRADIATED TUMOR-CELLS ENGINEERED TO SECRETE MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR STIMULATES POTENT, SPECIFIC, AND LONG-LASTING ANTITUMOR IMMUNITY
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DOI：
10.1073/pnas.90.8.3539
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
MULLIGAN, RC
中科院分区：
文献类型：
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作者：
DRANOFF, G;JAFFEE, E;MULLIGAN, RC
为了比较不同细胞因子及其他分子增强肿瘤细胞免疫原性的能力，我们构建了10种编码潜在免疫调节剂的逆转录病毒，并研究了经这些病毒转导的小鼠肿瘤细胞的疫苗特性。利用B16黑色素瘤模型（在此模型中，单独照射的肿瘤细胞不会激发显著的抗肿瘤免疫），我们发现表达小鼠粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）的照射肿瘤细胞激发了强大、持久且特异的抗肿瘤免疫，这种免疫需要CD4⁺和CD8⁺细胞。表达白细胞介素4和6的照射细胞也激发了可检测到的但较弱的活性。与B16系统相反，我们发现在许多其他肿瘤模型中，先前在涉及活的转导细胞的细胞因子基因转移研究中所报道的抗肿瘤免疫水平仅通过使用照射细胞就可达到。然而，通过调整疫苗或激发剂量，也能够在那些系统中证明小鼠GM - CSF的活性。总体而言，我们的结果对基因修饰肿瘤细胞作为治疗性癌症疫苗的临床应用具有重要意义。
To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4+ and CD8+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.