College of Bio-Medicine and Health, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
Hubei Cancer Hospital, Wuhan, Hubei, 430079, China.
Biochem Biophys Res Commun. 2020 May 7;525(3):607-613. doi: 10.1016/j.bbrc.2020.02.132. Epub 2020 Feb 27.
Personalized neoantigen vaccines are capable of eliciting vigorous T-cell responses and have been demonstrated to achieve striking therapeutic effects against cancer. Here we performed comprehensive mutanome analysis of the mouse Lewis lung cancer cells to identify tumor neoantigens followed by prediction of their MHC affinity and immunogenicity. We adopted a strategy that enables us to select neoantigens that were predicted to have high affinity to both MHC I and MHC II. Ten neoantigens were selected to synthesize peptide vaccines and tested in vivo for immunogenicity. Four neoantigen peptide vaccines were found to elicit robust immune reactivity and were further examined for tumor inhibition in mice with xenografted LLC tumors. Two neoantigen peptide vaccines showed significant inhibition on tumor growth and prolonged the survival of tumor-bearing mice. Our studies explored the neoantigen peptide vaccines to treat lung cancer and provide rationale for the optimization of tumor neoantigen selection for therapeutic vaccines.
个性化新抗原疫苗能够引发强烈的 T 细胞反应，并已被证明对癌症具有显著的治疗效果。在这里，我们对小鼠 Lewis 肺癌细胞进行了全面的突变组分析，以鉴定肿瘤新抗原，然后预测其 MHC 亲和力和免疫原性。我们采用了一种策略，使我们能够选择预测对 MHC I 和 MHC II 都具有高亲和力的新抗原。选择了 10 个新抗原来合成肽疫苗，并在体内测试其免疫原性。发现 4 种新抗原肽疫苗能够引发强烈的免疫反应，并进一步在携带异种移植 LLC 肿瘤的小鼠中检查其对肿瘤的抑制作用。两种新抗原肽疫苗显示出对肿瘤生长的显著抑制作用，并延长了荷瘤小鼠的存活时间。我们的研究探索了用新抗原肽疫苗治疗肺癌，并为优化治疗性疫苗的肿瘤新抗原选择提供了依据。
