用于个性化金属免疫治疗的自体癌症疫苗的生物矿化启发合成。
Biomineralization-inspired synthesis of autologous cancer vaccines for personalized metallo-immunotherapy.
发表日期:2024 Jul 19
作者:
Quguang Li, Yifan Yan, Chunjie Wang, Ziliang Dong, Yu Hao, Minming Chen, Zhuang Liu, Liangzhu Feng
来源:
GENES & DEVELOPMENT
摘要:
自体癌症疫苗代表了一种有前途的针对肿瘤复发的治疗方法。在此,开发了一种简洁的生物矿化策略,通过蛋白抗原介导的花状磷酸锰(MnP)纳米颗粒的生长来制备免疫刺激性自体癌症疫苗。除了继承了 Mn2 的环磷酸鸟苷-磷酸腺苷合酶 (cGAS) 激活干扰素基因 (STING) 的能力外,所得的负载卵清蛋白 (OVA) 的 MnP (OVA@MnP) 纳米粒子还具有优异的稳定性和 pH 值。反应性通过促进内切/溶酶体逃逸和随后的 OVA 抗原交叉呈递,能够有效启动抗原特异性 CD8 T 细胞扩增。结果,皮下接种后的 OVA@MnP 疫苗对表达 OVA 的 B16-F10 黑色素瘤具有预防和治疗作用。此外,由解剖肿瘤的完整肿瘤细胞裂解物制备的生物矿化自体癌症疫苗抑制了残留肿瘤的生长,特别是与抗PD-1免疫疗法相结合。这项研究强调了一种简单的生物矿化方法,用于可控合成 cGAS-STING 激活自体癌症疫苗,以抑制术后肿瘤复发。© 2024 作者。
Autologous cancer vaccines represent a promising therapeutic approach against tumor relapse. Herein, a concise biomineralization strategy was developed to prepare an immunostimulatory autologous cancer vaccine through protein antigen-mediated growth of flower-like manganese phosphate (MnP) nanoparticles. In addition to inheriting the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING)-activating capacity of Mn2+, the resulting ovalbumin (OVA)-loaded MnP (OVA@MnP) nanoparticles with superior stability and pH-responsiveness enabled efficient priming of antigen-specific CD8+ T cell expansion through promoting the endo/lysosome escape and subsequent antigen cross-presentation of OVA. Resultantly, OVA@MnP vaccines upon subcutaneous vaccination elicited both prophylactic and therapeutic effects against OVA-expressing B16-F10 melanoma. Furthermore, the biomineralized autologous cancer vaccines prepared from the whole tumor cell lysates of the dissected tumors suppressed the growth of residual tumors, particularly in combination with anti-PD-1 immunotherapy. This study highlights a simple biomineralization approach for the controllable synthesis of cGAS-STING-activating autologous cancer vaccines to suppress postsurgical tumor relapse.© 2024 The Authors.