Qilu Cell Therapy Technology Co., Ltd, Jinan, China.
Shandong Yinfeng Life Science Research Institute, Jinan, China.
Hum Vaccin Immunother. 2021 Nov 2;17(11):4363-4373. doi: 10.1080/21645515.2021.1955610. Epub 2021 Dec 1.
To deliver specific antigens in tumor immunotherapy, tumor cell lysates are commonly used to sensitize dendritic cells (DCs). However, the lysates possess low immunogenicity and contain many types of non-tumor-related antigens, which may induce autoimmune diseases. Tumor antigen peptides can provide high specificity but are expensive and their short half-lives limit their clinical application.
In this study, we used adenovirus to transfer the carbonic anhydrase IX (CA9) gene into DCs to generate specificity to renal cell carcinoma (RCC) which is the most common space-occupying lesion in humans. Inhibition of antigen presentation attenuators (iAPA) technology was also used to enhance the DC delivery capacity. Finally, DCs were co-cultured with cytotoxic T-lymphocytes (CTLs) and the anti-tumor effects were evaluated.
The results showed that the CA9-DC-CTLs possessed a high specificity to CA9-positive cells and showed stronger anti-tumor activity than GFP-DC-CTLs both and .
These findings may suggest a novel treatment option for RCC.
为了在肿瘤免疫治疗中递呈特定抗原,肿瘤细胞裂解物通常被用于致敏树突状细胞(DC)。然而,这些裂解物的免疫原性较低,且含有许多种非肿瘤相关抗原,这可能会引发自身免疫性疾病。肿瘤抗原肽可提供高度的特异性,但价格昂贵,且半衰期短,限制了其临床应用。
在这项研究中,我们使用腺病毒将碳酸酐酶 IX(CA9)基因转入 DC 以产生对肾细胞癌(RCC)的特异性,RCC 是人类最常见的占位性病变。我们还使用了抑制抗原呈递衰减器(iAPA)技术来增强 DC 的递呈能力。最后,我们将 DC 与细胞毒性 T 淋巴细胞(CTL)共培养,并评估其抗肿瘤效果。
结果表明,CA9-DC-CTL 对 CA9 阳性细胞具有高特异性,且其抗肿瘤活性强于 GFP-DC-CTL。
这些发现可能为 RCC 提供了一种新的治疗选择。