KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.
Chemical and Biomedical Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
Adv Sci (Weinh). 2024 Jul;11(25):e2308662. doi: 10.1002/advs.202308662. Epub 2024 Apr 26.
Cancer vaccines offer a promising avenue in cancer immunotherapy by inducing systemic, tumor-specific immune responses. Tumor extracellular vesicles (TEVs) are nanoparticles naturally laden with tumor antigens, making them appealing for vaccine development. However, their inherent malignant properties from the original tumor cells limit their direct therapeutic use. This study introduces a novel approach to repurpose TEVs as potent personalized cancer vaccines. The study shows that inhibition of both YAP and autophagy not only diminishes the malignancy-associated traits of TEVs but also enhances their immunogenic attributes by enriching their load of tumor antigens and adjuvants. These revamped TEVs, termed attenuated yet immunogenically potentiated TEVs (AI-TEVs), showcase potential in inhibiting tumor growth, both as a preventive measure and a possible treatment for recurrent cancers. They prompt a tumor-specific and enduring immune memory. In addition, by showing that AI-TEVs can counteract cancer growth in a personalized vaccine approach, a potential strategy is presented for developing postoperative cancer immunotherapy that's enduring and tailored to individual patients.
癌症疫苗通过诱导全身、肿瘤特异性免疫反应,为癌症免疫治疗提供了一个有前途的途径。肿瘤细胞外囊泡(TEVs)是天然负载肿瘤抗原的纳米颗粒,使其成为疫苗开发的理想选择。然而,它们源自原始肿瘤细胞的固有恶性特性限制了其直接治疗用途。本研究提出了一种将 TEVs 重新用于强效个性化癌症疫苗的新方法。研究表明,抑制 YAP 和自噬不仅可以降低 TEVs 的恶性相关特征,还可以通过丰富其肿瘤抗原和佐剂负载来增强其免疫原性属性。这些经过改良的 TEVs,称为减弱但免疫增强的 TEVs(AI-TEVs),在抑制肿瘤生长方面具有潜力,无论是作为预防措施还是治疗复发性癌症的可能方法。它们引发了肿瘤特异性和持久的免疫记忆。此外,通过表明 AI-TEVs 可以通过个性化疫苗方法对抗癌症生长,提出了一种潜在的策略,用于开发持久且针对个体患者的术后癌症免疫治疗。