Synergistic Activation of Antitumor Immunity by a Particulate Therapeutic Vaccine.
Synergistic Activation of Antitumor Immunity by a Particulate Therapeutic Vaccine.
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通过颗粒治疗疫苗对抗肿瘤免疫的协同激活。
DOI：
10.1002/advs.202100166
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Shen H
中科院分区：
文献类型：
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作者：
Mai J;Li Z;Xia X;Zhang J;Li J;Liu H;Shen J;Ramirez M;Li F;Li Z;Yokoi K;Liu X;Mittendorf EA;Ferrari M;Shen H
抗癌免疫治疗的成功依赖于刺激肿瘤抗原特异性T淋巴细胞和T细胞有效浸润肿瘤组织。在这里，描述了一种治疗性疫苗，其促进抗原特异性T细胞在发炎和非发炎肿瘤类型中的增殖和肿瘤浸润。该疫苗由STING激动剂2′3′-cGAMP、TLR 9配体CpG和加载到纳米多孔微粒（μGCVax）中的肿瘤抗原肽组成。μGCVax在各自的小鼠模型中可有效抑制肺转移性黑色素瘤、原发性乳腺癌和皮下结直肠癌，包括HER 2阳性乳腺癌的功能性治愈。在机制上，μGCVax有效刺激树突状细胞中I型干扰素的表达，并促进CD 8+和CD 103+树突状细胞成熟和迁移到淋巴结和其他淋巴组织。抗肿瘤应答依赖于TLR 9和干扰素α/β受体信号传导，并且在较小程度上依赖于STING信号传导。这些结果表明，μGCVax在个性化癌症治疗中介导抗肿瘤免疫的潜力很大。佐剂活性是治疗性癌症疫苗效力的关键。在这篇文章中，描述了可溶性和颗粒佐剂的组合，通过促进I型干扰素和其他炎性细胞因子协同和有效地刺激树突状细胞，导致抗原特异性细胞毒性T细胞的稳健活化和随后的疫苗抗肿瘤免疫。
Success in anticancer immune therapy relies on stimulation of tumor antigen‐specific T lymphocytes and effective infiltration of the T cells into tumor tissue. Here, a therapeutic vaccine that promotes proliferation and tumor infiltration of antigen‐specific T cells in both inflamed and noninflamed tumor types is described. The vaccine consists of STING agonist 2′3′‐cGAMP, TLR9 ligand CpG, and tumor antigen peptides that are loaded into nanoporous microparticles (μGCVax). μGCVax is effective in inhibiting lung metastatic melanoma, primary breast cancer, and subcutaneous colorectal cancer in their respective murine models, including functional cure of HER2‐positive breast cancer. Mechanistically, μGCVax potently stimulates type I interferon expression in dendritic cells, and promotes CD8+ and CD103+ dendritic cell maturation and migration to lymph nodes and other lymphatic tissues. Antitumor responses are dependent on TLR9 and interferon α/β receptor signaling, and to a less extent on STING signaling. These results demonstrate a high potential for μGCVax in mediating antitumor immunity in personalized cancer therapy. Adjuvant activity is key for potency of a therapeutic cancer vaccine. In this article, a combination of soluble and particulate adjuvants is described that synergistically and potently stimulates dendritic cells by promoting type I interferons and other inflammatory cytokines, leading to robust activation of antigen‐specific cytotoxic T cells and consequent antitumor immunity from the vaccine.
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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
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
7.2
作者：
Charles，Julie;Chaperot，Laurence;Plumas，Joel
通讯作者：
Plumas，Joel
影响因子：
15.9
作者：
Hanson, Melissa C.;Crespo, Monica R.;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
30.5
作者：
通讯作者：
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