Effects of Combinatorial Ubiquitinated Protein-Based Nanovaccine and STING Agonist in Mice With Drug-Resistant and Metastatic Breast Cancer.
Effects of Combinatorial Ubiquitinated Protein-Based Nanovaccine and STING Agonist in Mice With Drug-Resistant and Metastatic Breast Cancer.
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DOI：
10.3389/fimmu.2021.707298
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Huang F;Pan N;Wei Y;Zhao J;Aldarouish M;Wang X;Sun X;Wen Z;Chen Y;Wang L
我们以前报道过，从肿瘤细胞中富集的泛素化蛋白（UPs）有可能用作抗肿瘤的免疫治疗疫苗。本研究从表阿霉素（EPB）诱导的多药耐药乳腺癌干细胞样细胞系（4 T1/EPB）中富集UPs，并检测α-Al 2 O3-UPs-4 T1/EPB（简称UPs-4 T1/EPB）单独作为治疗性疫苗以及与干扰素基因刺激因子（STING）激动剂联合作为治疗性疫苗在耐药和转移性乳腺癌小鼠中的疗效。用UPs-4 T1/EPB疫苗接种通过增强特异性CD 8 + T细胞应答和扩增肿瘤浸润淋巴细胞（TIL）的T细胞受体多样性而发挥深刻的抗肿瘤作用。重要的是，与STING激动剂的组合进一步促进了成熟CD 8 α+树突状细胞向淋巴结的迁移和肿瘤内TIL的浸润，导致小鼠中的原发性肿瘤消退和肺转移根除。此外，治愈的小鼠对随后用相同肿瘤进行的再激发具有完全抗性。我们的研究表明，这种新型的UPs-4 T1/EPB疫苗和STING激动剂的组合免疫疗法在耐药和转移性乳腺癌小鼠中是有效的。
We previously reported that enriched ubiquitinated proteins (UPs) from tumor cells have the potential to be used as immunotherapy vaccine against cancer. Here we enriched UPs from epirubicin (EPB)-induced multi-drug-resistant cancer stem-like breast cancer cell line (4T1/EPB) and tested the efficacy of α-Al2O3-UPs-4T1/EPB (short for UPs-4T1/EPB) as therapeutic vaccine alone and in combination with the stimulator of interferon genes (STING) agonist in mice with drug-resistant and metastatic breast cancer. Vaccination with UPs-4T1/EPB exerted profound anti-tumor effects through augmented specific CD8+ T cell responses and amplified T cell receptor diversity of tumor-infiltrating lymphocytes (TILs). Importantly, the combination with STING agonist further facilitated the migration of mature CD8α+ dendritic cells to the lymph nodes and the infiltration of TILs within tumors, resulting in primary tumor regression and pulmonary metastasis eradication in mice. Moreover, the cured mice were completely resistant against a subsequent rechallenge with the same tumor. Our study indicates that this novel combinatorial immunotherapy with UPs-4T1/EPB vaccine and STING agonist is effective in mice with drug-resistant and metastatic breast cancer.
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影响因子：
8.8
作者：
Corrales L;Glickman LH;McWhirter SM;Kanne DB;Sivick KE;Katibah GE;Woo SR;Lemmens E;Banda T;Leong JJ;Metchette K;Dubensky TW Jr;Gajewski TF
通讯作者：
Gajewski TF
靶向CD8 T细胞免疫的最新进展，以实现更有效的癌症免疫疗法。
影响因子：
7.3
作者：
Durgeau A;Virk Y;Corgnac S;Mami-Chouaib F
通讯作者：
Mami-Chouaib F
基于自噬体的 HBV 感染治疗疫苗：临床前评估
影响因子：
7.4
作者：
Xue M;Fan F;Ding L;Liu J;Su S;Yin P;Cao M;Zhao W;Hu HM;Wang L
通讯作者：
Wang L
影响因子：
5.2
作者：
Chiodi I;Belgiovine C;Donà F;Scovassi AI;Mondello C
通讯作者：
Mondello C
最前沿：T 细胞中 STING 的激活可诱导 I 型 IFN 反应和细胞死亡。
DOI：
10.4049/jimmunol.1601999
发表时间：
2017-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Larkin B;Ilyukha V;Sorokin M;Buzdin A;Vannier E;Poltorak A
通讯作者：
Poltorak A