LADS: a powerful vaccine platform for cancer immunotherapy and prevention.

IF 4.4 1区 生物学 Q1 BIOLOGY
Jing Sun, Jing Wang, Xin Jiang, Jing Xia, Yue Han, Mianmian Chen, Jiali Xu, Simin Deng, Changyong Cheng, Houhui Song
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Abstract

Background: The intracellular bacterium Listeria monocytogenes is an attractive vector for cancer immunotherapy as it can effectively deliver tumor antigens to antigen-presenting cells, leading to a robust antitumor response.

Results: In this study, we developed a novel vaccine platform called Listeria-based Live Attenuated Double Substitution (LADS), which involves introducing two amino acid substitutions (N478AV479A) into the virulence factor listeriolysin O (LLO). LADS is a safe vaccine platform, with an attenuation of nearly 7000-fold, while retaining complete immunogenicity due to the absence of deletion of any virulence factors. We developed two LADS-based vaccines, LADS-E7 and LADS-AH1, which deliver the human papillomavirus (HPV) type 16 E7 oncoprotein and murine colon carcinoma immunodominant antigen AH1, respectively. Treatment with LADS-E7 or LADS-AH1 significantly inhibited and regressed established tumors, while also dramatically increasing the populations of tumor-infiltrated antigen-specific CD8+ T cells. RNA-sequencing analysis of tumor tissue samples revealed that LADS-E7 altered the expression of genes related to the immune response. Moreover, intratumoral injection of LADS-based vaccines induced strong antitumor responses, generating systemic antitumor responses to control distant tumor growth. Encouragingly, LADS-E7 or LADS-AH1 immunization effectively prevented tumor formation and growth.

Conclusions: Our findings demonstrate that LADS-based vaccines represent a more powerful platform for the development of immunotherapeutic and preventive vaccines against cancers and infectious diseases.

LADS:癌症免疫治疗和预防的强大疫苗平台。
背景:单核细胞增生李斯特菌是一种有吸引力的肿瘤免疫治疗载体,因为它可以有效地将肿瘤抗原传递到抗原呈递细胞,从而产生强大的抗肿瘤反应。结果:在本研究中,我们开发了一种新的疫苗平台,称为基于李斯特菌的活减毒双替代(LADS),该平台将两个氨基酸取代(N478AV479A)引入毒力因子李斯特菌溶素O (LLO)中。LADS是一种安全的疫苗平台,衰减近7000倍,同时由于没有删除任何毒力因子而保持完全的免疫原性。我们开发了两种基于lads的疫苗,LADS-E7和LADS-AH1,它们分别递送人乳头瘤病毒(HPV) 16型E7癌蛋白和小鼠结肠癌免疫优势抗原AH1。用LADS-E7或LADS-AH1治疗可显著抑制和消退已建立的肿瘤,同时也显著增加肿瘤浸润抗原特异性CD8+ T细胞的数量。肿瘤组织样本的rna测序分析显示,LADS-E7改变了与免疫应答相关的基因的表达。此外,肿瘤内注射基于lads的疫苗可诱导强烈的抗肿瘤反应,产生全身抗肿瘤反应以控制远处肿瘤的生长。令人鼓舞的是,LADS-E7或LADS-AH1免疫有效地阻止了肿瘤的形成和生长。结论:我们的研究结果表明,基于lads的疫苗为开发针对癌症和传染病的免疫治疗和预防性疫苗提供了一个更强大的平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
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