The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Department of Oncology, Rudong Peoples' Hospital of Jiangsu Province, Nantong, China.
Cancer Sci. 2021 Nov;112(11):4490-4500. doi: 10.1111/cas.15145. Epub 2021 Sep 27.
Various cancer vaccines have been developed to generate and amplify antigen-specific T cell responses against malignancy. Among them, in situ vaccination is one of the most practical types as it can trigger immune responses without previous antigen identification. Here we reported a novel in situ vaccine by intratumoral injection of imiquimod and OX40 agonist. In mice bearing hepatic carcinoma, both the injected tumor and the noninjected tumor in the distant lesion of the same mice were suppressed after vaccination. Further studies found that this in situ vaccine triggered systemic tumor-specific responses, with one-fold increase of effector memory T cells properties and stronger toxicity of lymphocytes in spleen. Besides, we found that imiquimod upregulated the expression of OX40 on CD4 T cells and thus enhanced the effectiveness of OX40 agonist. Five immune-positive-related pathways were activated after vaccination. This in situ vaccine caused little harm to normal organs and provided long-term protection against the same syngeneic tumor rechallenge. Due to its effectiveness, feasibility and safety, this strategy could potentially be applied to various types of late-stage solid tumors and worthy of further clinical research.
已经开发了各种癌症疫苗来产生和扩增针对恶性肿瘤的抗原特异性 T 细胞反应。其中，原位疫苗是最实用的类型之一，因为它可以在无需预先识别抗原的情况下引发免疫反应。在这里，我们报道了一种通过瘤内注射咪喹莫特和 OX40 激动剂的新型原位疫苗。在荷肝癌小鼠中，接种后注射肿瘤和同一小鼠远处未注射肿瘤均受到抑制。进一步的研究发现，这种原位疫苗引发了全身肿瘤特异性反应，效应记忆 T 细胞特性增加了一倍，脾脏淋巴细胞的毒性更强。此外，我们发现咪喹莫特上调了 CD4 T 细胞上 OX40 的表达，从而增强了 OX40 激动剂的有效性。接种后有五个免疫阳性相关通路被激活。这种原位疫苗对正常器官几乎没有伤害，并能为同种同源肿瘤再挑战提供长期保护。由于其有效性、可行性和安全性，该策略有可能应用于各种晚期实体肿瘤，并值得进一步的临床研究。
