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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
STING 激动剂 2'3'-cGAMP 作为 HPV16 肽疫苗的有效佐剂增强 TC-1 小鼠模型中的抗肿瘤免疫
英文原题：STING agonist 2'3'-cGAMP as an effective adjuvant for HPV16 peptide vaccine enhances anti-tumor immunity in TC-1 mice models.
查看英文原题
STING agonist 2'3'-cGAMP as an effective adjuvant for HPV16 peptide vaccine enhances anti-tumor immunity in TC-1 mice models.
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研究概要
STING 激动剂 2'3'-cGAMP 作为一种有效佐剂，可增强 HPV16 肽疫苗的治疗效果。这些发现表明其有潜力成为 HPV16 持续感染及相关恶性肿瘤的候选治疗药物。
研究思路结论见上方概要
背景
佐剂对于增强疫苗免疫原性至关重要。环鸟苷酸-腺苷酸合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路中的激动剂已在临床前模型中显示出强大的免疫激活作用。靶向高危型人乳头瘤病毒（HPV）E6和E7的T细胞表位的肽疫苗是一种有前景的免疫策略。为提高免疫原性，我们使用STING激动剂2'3'-cGAMP作为佐剂，并评估其增强免疫应答和抗肿瘤疗效的能力。
方法
以2'3'-cGAMP为佐剂的HPV16 E7 43-77肽候选疫苗在不同初始肿瘤大小（直径2-3 mm和5-6 mm）的已建立TC-1肿瘤移植模型中的免疫原性和疗效进行了评估。荷瘤小鼠每周接受三次瘤周皮下疫苗接种。在体外和体内研究了其对肿瘤抑制、抗原特异性细胞毒性T淋巴细胞（CTL）反应诱导及相关免疫机制的影响。
结果
用2'3'-cGAMP佐剂的E7 43-77肽免疫显著抑制了肿瘤生长，并在CD8+细胞毒性T淋巴细胞中诱导了高水平干扰素（IFN）-γ和颗粒酶B。该疫苗还增强了自然杀伤（NK）细胞、树突状细胞（DCs）和M1型巨噬细胞的分化，减少了髓源性抑制细胞（MDSCs），增加了INF-β水平，并促进肿瘤免疫微环境（TME）中的淋巴细胞浸润和重塑。在机制上，2'3'-cGAMP通过激活肽负载DCs中的STING-TBK1-IRF3和STING-NF-κB通路，促进DC成熟，增强T细胞增殖和活化，并加强抗原特异性CTL反应。
展开英文摘要原文
BACKGROUND
Adjuvants are critical for enhancing vaccine immunogenicity. The agonists in cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway have demonstrated robust immune activation in preclinical models. Peptide vaccines targeting T cell epitopes of high-risk human papillomavirus (HPV) E6 and E7 represent a promising immunization strategy. To improve immunogenicity, we utilized the STING agonist 2'3'-cGAMP as an adjuvant and evaluated its ability to enhance immune responses and antitumor efficacy.
METHODS
The immunogenicity and efficacy of a candidate vaccine, consisting of the HPV16 E7 43-77 peptide adjuvanted with 2'3'-cGAMP, were evaluated in established TC-1 tumor transplantation models with different initial tumor sizes (2-3 mm and 5-6 mm in diameter). Tumor-bearing mice received three weekly peritumoral subcutaneous vaccine doses. The effects on tumor suppression, antigen-specific cytotoxic T lymphocyte (CTL) response induction, and related immune mechanisms were investigated both in vitro and in vivo .
RESULTS
Immunization with the E7 43-77 peptide adjuvanted by 2'3'-cGAMP significantly suppressed tumor growth and elicited high levels of Interferon (IFN)-γ and Granzyme B in CD8 + cytotoxic T lymphocytes. The vaccine also enhanced the differentiation of natural killer (NK) cells, dendritic cells (DCs), and M1-type macrophages, reduced Myeloid-derived suppressor cells (MDSCs), and increased INF-β levels, as well as promote lymphocyte infiltration and remodeling in tumor immune microenvironment (TME). Mechanistically, 2'3'-cGAMP promoted DC maturation, enhanced T cell proliferation and activation, and strengthened antigen-specific CTL responses by activating the STING-TBK1-IRF3 and STING-NF-κB pathways in peptide-loaded DCs.
CONCLUSION
The STING agonist 2'3'-cGAMP serves as an effective adjuvant that enhances the therapeutic efficacy of an HPV16 peptide vaccine. These findings indicate its potential as a candidate therapeutic for HPV16 persistent infection and associated malignancies.
论文信息
- 作者
- Cun Y、Yang R、Dai J、Zhang X、Zhou L、Shi L、Li J、He H
- 第一作者单位
- Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, China.China
- 通讯作者单位
- Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, China.China
- 期刊
- Frontiers in cellular and infection microbiology2026
- 原文标识
- PubMed 42394822 · DOI 10.3389/fcimb.2026.1798489
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