A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8+ T cells in solid tumours.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Nanobiotechnology Pub Date : 2024-10-19 DOI:10.1186/s12951-024-02914-6
Meng-Jie Jiang, Hao-Peng Cui, Ting-Ting Li, Xiao-Mei Yang, Xiao-Ling Lu, Ai-Qun Liu
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Abstract

Background: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions.

Results: The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts.

Conclusion: Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

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新型抗CTLA-4纳米体-IL12融合蛋白与树突状细胞/肿瘤融合细胞疫苗相结合,可增强CD8+T细胞在实体瘤中的抗肿瘤活性。
背景:我们之前开发了一种靶向 CTLA-4 的纳米抗体,并证明它能在体外增强抗肿瘤 T 细胞反应;然而,将 T 细胞注射到癌症模型后产生的反应通常较弱且短暂。在此,我们探讨了将纳米抗体与IL-12融合是否能使其在暴露于未成熟树突状细胞和肿瘤细胞融合后诱导更强、更持久的T细胞免疫反应:结果:融合蛋白在体外增强了CD8+ T细胞对肿瘤抗原的反应,并在T细胞被注射到携带不同类型异种移植物的小鼠体内后产生了更强、更持久的免疫反应:我们的体外和体内研究结果表明,我们的纳米抗体-白细胞介素融合系统具有抗癌潜力,并支持将这种融合方法用于各种纳米抗体的临床应用。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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