研究概要
这些发现表明 aAVC-TAA/CoV-2-S 疗法作为一种有前景的疫苗候选,可用于预防 COVID-19,并增强癌症治疗的效果。
中文摘要
当前2019冠状病毒病(COVID-19)疫苗的疗效已得到证实;然而,新出现的证据表明,在某些免疫功能受损的癌症患者中保护不足。我们此前开发了一种基于细胞的抗癌疫苗平台,涉及人工佐剂载体细胞(aAVCs),能够通过增强先天免疫来诱导强烈的适应性反应。aAVCs是转染靶抗原的同种异体细胞,其表面同时表达自然杀伤T细胞配体-CD1d复合物。在本研究中,我们应用该系统靶向严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白(CoV-2-S),使用表达CoV-2-S的aAVCs(aAVC-CoV-2),并在小鼠模型中评估了免疫反应。单剂aAVC-CoV-2诱导了大量CoV-2-S特异性多功能CTLs,以及CD4+ T细胞依赖性抗CoV-2-S特异性Abs。CoV-2-S特异性CTLs浸润肺实质并作为长期记忆T细胞持续存在。此外,我们用共表达CoV-2-S和肿瘤相关抗原(TAA)的aAVCs(aAVC-TAA/CoV-2)免疫小鼠,并评估是否引发了抗SARS-CoV-2和抗肿瘤CTLs。我们发现aAVC-TAA/CoV-2-S治疗发挥了明显的抗肿瘤效果并诱导了CoV-2-S特异性CTLs。这些发现表明aAVC-TAA/CoV-2-S治疗是一种有前景的疫苗候选方案,可用于预防COVID-19以及增强癌症治疗的疗效。
展开英文摘要原文
The efficacy of current coronavirus disease 2019 (COVID-19) vaccines has been demonstrated; however, emerging evidence suggests insufficient protection in certain immunocompromised cancer patients. We previously developed a cell-based anti-cancer vaccine platform involving artificial adjuvant vector cells (aAVCs) capable of inducing a strong adaptive response by enhancing the innate immunity. aAVCs are target antigen-transfected allogenic cells that simultaneously express the natural killer T-cell ligand-CD1d complex on their surface. In the present study, we applied this system for targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (CoV-2-S) using CoV-2-S-expressing aAVCs (aAVC-CoV-2) and evaluated the immune response in a murine model. A single dose of aAVC-CoV-2 induced a large amount of CoV-2-S-specific, multifunctional CTLs in addition to CD4 + T-cell-dependent anti-CoV-2-S-specific Abs. CoV-2-S-specific CTLs infiltrated the lung parenchyma and persisted as long-term memory T cells. Furthermore, we immunized mice with CoV-2-S- and tumor-associated antigen (TAA)-co-expressing aAVCs (aAVC-TAA/CoV-2) and evaluated whether the anti-SARS-CoV-2 and antitumor CTLs were elicited. We found that the aAVC-TAA/CoV-2-S therapy exerted apparent antitumor effects and induced CoV-2-S-specific CTLs. These findings suggest aAVC-TAA/CoV-2-S therapy as a promising vaccine candidate for preventing COVID-19, as well as enhancing the effectiveness of cancer therapies.
论文信息
- 作者
- Shimizu K、Ueda S、Kawamura M、Satoh M、Fujii SI
- 单位
- Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.Japan
- 期刊
- Cancer science2022 Aug