肿瘤细胞治疗研究
英文原题：The Dendritic Cell-based Vaccine PROTEXI leverages Antiviral CD4 T cell Memory to boost anti-tumor immune responses in mice.
DC 癌症疫苗的疗效与肿瘤相关抗原免疫原性差以及未能引发强效的 MHC II 类限制性 CD4 T 细胞反应有关。
树突状细胞（DC）癌症疫苗的疗效与肿瘤相关抗原免疫原性差以及无法引发强效的MHC II类限制性CD4 T细胞应答有关。在此，我们介绍PROTEXI，一种DC疫苗平台，通过将肿瘤特异性CD8 T细胞表位与来自SARS-CoV-2 Spike蛋白的CD4 T辅助表位共同呈递，利用广泛存在的抗病毒免疫，从而优化肿瘤免疫。在黑色素瘤和乳腺癌的临床前小鼠模型中，PROTEXI通过促进强效T细胞浸润进入免疫冷肿瘤、经由表位扩展增强细胞毒性T细胞应答，以及激活与最佳DC、NK细胞和T细胞功能相关的基因，显著减缓肿瘤生长并改善生存。此外，在治疗耐药肿瘤模型中，PROTEXI与其他免疫治疗药物联合时引发更优的应答。最后，在黑色素瘤人源化小鼠模型中，PROTEXI疫苗将CD4 T特异性Spike表位与CD8 T细胞限制性PRAME和MAGE-A3抗原共同呈递，显著降低肿瘤负荷。因此，这些数据凸显了利用预先存在的病毒特异性免疫来增强DC疫苗在免疫冷肿瘤中疗效的潜力。
The efficacy of dendritic cell (DC) cancer vaccines is linked to poor immunogenicity of tumor-associated antigens and failure to elicit robust MHC class II-restricted CD4 T-cell responses. Here, we introduce PROTEXI, a DC vaccine platform that optimizes tumor immunity by co-presenting tumor-specific CD8 T-cell epitopes alongside CD4 T helper epitopes from the SARS-CoV-2 Spike protein, leveraging widespread anti-viral immunity. In preclinical mouse models of melanoma and breast cancer, PROTEXI significantly reduces tumor growth and improves survival by promoting robust T cell infiltration into immune-cold tumors, increasing cytotoxic T cell responses via epitope spreading, and activating genes linked to optimal DC, NK cell, and T cell function. Furthermore, PROTEXI elicits superior responses when combined with other immunotherapy agents in models of therapy-resistant tumors. Finally, in a humanized mouse model of melanoma, PROTEXI vaccine co-presenting CD4 T-specific Spike epitopes with CD8 T cell-restricted PRAME and MAGE-A3 antigens, significantly reduces tumor burden. Thus, these data underscore the potential of harnessing pre-existing viral-specific immunity to enhance the efficacy of DC vaccines in immune-cold tumors.
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