皮内接种植物糖原纳米颗粒和 STING 激动剂可诱导细胞毒性 T 淋巴细胞介导的抗肿瘤免疫。
Intradermal vaccination with a phytoglycogen nanoparticle and STING agonist induces cytotoxic T lymphocyte-mediated antitumor immunity.
发表日期:2024 Aug 17
作者:
Juan F Hernandez-Franco, Imran M Jan, Bennett D Elzey, Harm HogenEsch
来源:
npj Vaccines
摘要:
癌症疫苗开发的一个关键方面是有效佐剂的配方。本研究评估了将阳离子植物源纳米颗粒佐剂 (Nano-11) 与经过临床测试的 STING 激动剂 ADU-S100 (MIW815) 相结合是否可以通过皮内疫苗接种刺激抗癌免疫力。 Nano-11 与 ADU-S100 (NanoST) 结合可协同激活抗原呈递细胞,促进蛋白质抗原在体外和体内的交叉呈递。使用卵清蛋白 (OVA) 作为肿瘤抗原并结合 Nano-11 或 NanoST 进行皮内疫苗接种可预防小鼠 B16-OVA 黑色素瘤和 E.G7-OVA 淋巴瘤肿瘤的发展。 CD8 T 细胞消除会消除抗肿瘤免疫,但 CD4 T 细胞消除不会消除抗肿瘤免疫。 NanoST 治疗性疫苗接种可通过抑制 B16-OVA 肿瘤生长来提高小鼠的存活率,并且通过 PD-1 检查点阻断进一步增强这种效果。我们的研究为开发 NanoST 作为皮内疫苗接种佐剂以及通过 STING 靶向激活开发下一代预防性和治疗性癌症疫苗提供了强有力的理由。© 2024。作者。
A critical aspect of cancer vaccine development is the formulation with effective adjuvants. This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination. Nano-11 combined with ADU-S100 (NanoST) synergistically activated antigen-presenting cells, facilitating protein antigen cross-presentation in vitro and in vivo. Intradermal vaccination using ovalbumin (OVA) as a tumor antigen and combined with Nano-11 or NanoST prevented the development of murine B16-OVA melanoma and E.G7-OVA lymphoma tumors. The antitumor immunity was abolished by CD8+ T cell depletion but not by CD4+ T cell depletion. Therapeutic vaccination with NanoST increased mouse survival by inhibiting B16-OVA tumor growth, and this effect was further enhanced by PD-1 checkpoint blockade. Our study provides a strong rationale for developing NanoST as an adjuvant for intradermal vaccination and next-generation preventative and therapeutic cancer vaccines by STING-targeted activation.© 2024. The Author(s).