State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Adv Sci (Weinh). 2023 Jul;10(20):e2300418. doi: 10.1002/advs.202300418. Epub 2023 May 10.
Cancer vaccines have shown promise as effective means of antitumor immunotherapy by inducing tumor antigen-specific T cell immunity. In this study, a novel peptide-based tumor nanovaccine that boosts antigen presentation and elicits effective antitumor immunity is developed. The adjuvant characteristics of an antimicrobial peptide-derived core peptide, FK-13, are investigated and used it to generate a fusion peptide named FK-33 with tumor antigen epitopes. l-phenylalanine-based poly(ester amide) (Phe-PEA), 8p4, is also identified as a competent delivery vehicle for the fusion peptide FK-33. Notably, the vaccination of 8p4 + FK-33 nanoparticles (8FNs) in vivo induces dendritic cell activation in the lymph nodes and elicits robust tumor antigen-specific CD8 T cell response. The nanovaccine 8FNs demonstrate significant therapeutic and prophylactic efficacy against in situ tumor growth, effectively inhibit tumor metastasis, and significantly prolong the survival of tumor-bearing mice. Moreover, 8FNs can incorporate different tumor antigens and exhibit a synergistic therapeutic effect with antiprogrammed cell death protein 1 (PD-1) therapy. In summary, 8FNs represent a promising platform for personalized cancer vaccines and may serve as a potential combinational modality to improve current immunotherapy.
癌症疫苗通过诱导肿瘤抗原特异性 T 细胞免疫,已显示出作为抗肿瘤免疫疗法的有效手段的潜力。在这项研究中,开发了一种新型基于肽的肿瘤纳米疫苗,可增强抗原呈递并引发有效的抗肿瘤免疫。研究了一种抗菌肽衍生核心肽 FK-13 的佐剂特性,并将其用于生成具有肿瘤抗原表位的融合肽 FK-33。基于 l-苯丙氨酸的聚(酯酰胺)(Phe-PEA)8p4 也被鉴定为融合肽 FK-33 的有效递药载体。值得注意的是,体内接种 8p4+FK-33 纳米颗粒(8FNs)可在淋巴结中诱导树突状细胞激活,并引发强烈的肿瘤抗原特异性 CD8 T 细胞反应。纳米疫苗 8FNs 对原位肿瘤生长具有显著的治疗和预防功效,有效抑制肿瘤转移,并显著延长荷瘤小鼠的存活时间。此外,8FNs 可纳入不同的肿瘤抗原,并与抗程序性细胞死亡蛋白 1(PD-1)治疗具有协同治疗作用。总之,8FNs 代表了个性化癌症疫苗的有前途的平台,并且可能作为一种潜在的联合方式来改善当前的免疫疗法。
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