Science2014-06-10 4:03 PM

美科学家发现突变特异性T细胞反应能够有效抵抗癌症 Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer

论文摘要 

据一项新的报告显示,对肿瘤细胞所表达的一种突变能特异性识别的T细胞在一个罹患上皮细胞癌的病人中显示了抗癌活性。恶性肿瘤有着基因改变——过继性T细胞治疗就是利用了其中的某个特征。

过继性T细胞疗法指的是那些在体外增加免疫衍生细胞——如淋巴细胞——的数目并接着将这些细胞转移回病人体内以增进其免疫力的疗法。最近,随着对某些带有特定突变的恶性肿瘤的了解,科学家们制备了能特异性识别这些突变的T细胞--并接着将它们灌注回病人体内以产生一种抗肿瘤免疫反应。

尽管在黑色素瘤中已经看到了治疗的裨益,但人类免疫系统是否能发起一种针对上皮细胞癌的对突变具有特异性的T细胞反应则仍不清楚;上皮细胞癌常常比黑色素瘤所含的突变要少,但它们却占了所有人类恶性肿瘤中的80%以上。

如今,应用全外显子组测序,eric Tran等人确定了肿瘤浸润性CD4+ T细胞,这些T细胞对某罹患被称为胆管癌的上皮细胞癌患者的肿瘤所表达的一个突变基因具有特异性;该患者的胆管癌已经扩散到了肝与肺。对该患者输注数目得到扩增的对该突变具有特异性的T细胞导致了肿瘤的消退及病情的稳定。此外,用一群高纯度的该细胞治疗后所见的肿瘤消退证实了突变特异性T细胞介导了该肿瘤消退。

由Tran及其同事所做的工作提示,由免疫系统发动的突变特异性t细胞反应会在某一天被用来研发有效的个性化癌症免疫疗法。


Abstract 

Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive TH1 cells and again experienced tumor regression. These results provide evidence that a CD4+ T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer.

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