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开发一种多功能癌症疫苗格式,针对抗原呈现细胞,使用基于近距离的sortase A介导的T细胞内皮质的结合

Aru Z Wang^1,2,3, Hendrik J Brink^1,2,3, Rianne G Bouma^1,2,3

¹Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Bioconjugate chemistry

|November 8, 2024

概括

这项研究提出了一个新的癌症疫苗平台,使用基于近距离的Sortase A介导结合 (PBSL). 这种多功能格式迅速结合了患者特定的瘤抗原,以增强对癌症的免疫反应.

科学领域:

免疫学免疫学免疫学
生物技术是生物技术.
在瘤学瘤学.

背景情况:

癌症疫苗旨在增强抗瘤免疫力,特别是在对检查点抑制剂无反应的患者中.
使用患者特异性抗原的个性化癌症疫苗非常有效,但生产起来很复杂.
针对具有特定受体的抗原呈现细胞 (APC),如DEC205和CD169,可以增强免疫刺激.

研究的目的:

开发一种多功能癌症疫苗平台,使瘤抗原的特定位点结合成为可能.
利用基于近距离的Sortase A介导结合 (PBSL) 来对抗原与APC向抗体进行附着.
创建一种快速且可适应的方法来合成个性化癌症疫苗.

主要方法:

改造的小鼠IgG2a抗体针对DEC205或CD169,包含Sortase A (SrtA) 动机和SpyTag.
使用SrtA-SpyCatcher系统进行基于SrtA介导的抗原 (FITC或) 与抗体的近距离结合.
用CRISPR/HDR进行抗体工程,并评估抗体结合和免疫刺激in vitro和in vivo.

主要成果:

使用PBSL方法成功将抗原与DEC205和CD169特异性抗体结合起来.
证明结合抗体有效地与表达DEC205的树突细胞和表达CD169的巨细胞结合在体外和体内.
表明用这些抗体-抗原结合物的免疫有效地刺激了T细胞 in vivo 的反应.

结论:

开发了一种使用PBSL进行快速抗原结合的新型癌症疫苗格式.
该平台使瘤抗原与APC向抗体的特定位点结合成为可能.
这种方法对个性化癌症疫苗的高效合成具有前途.

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