Department of NanoEngineering, University of California-San Diego, La Jolla, CA 92039, USA.
Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106, USA.
Biomater Sci. 2020 Sep 30;8(19):5489-5503. doi: 10.1039/d0bm01219j.
The immunosuppressive tumor microenvironment enables cancer to resist immunotherapies. We have established that intratumoral administration of plant-derived Cowpea mosaic virus (CPMV) nanoparticles as an in situ vaccine overcomes the local immunosuppression and stimulates a potent anti-tumor response in several mouse cancer models and canine patients. CPMV does not infect mammalian cells but acts as a danger signal that leads to the recruitment and activation of innate and subsequently, adaptive immune cells. In the present study we addressed whether other icosahedral viruses or virus-like particles (VLPs) of plant, bacteriophage and mammalian origin can be similarly employed as intratumoral immunotherapy. Our results indicate that CPMV in situ vaccine outperforms Cowpea chlorotic mottle virus (CCMV), Physalis mosaic virus (PhMV), Sesbania mosaic virus (SeMV), bacteriophage Qβ VLPs, or Hepatitis B virus capsids (HBVc). Furthermore, ex vivo and in vitro assays reveal unique features of CPMV that makes it an inherently stronger immune stimulant.
免疫抑制性肿瘤微环境使癌症能够抵抗免疫疗法。我们已经证实,在肿瘤内给予植物源性豇豆花叶病毒(CPMV)纳米颗粒作为原位疫苗,可以克服局部免疫抑制,并在几种小鼠癌症模型和犬科患者中刺激强烈的抗肿瘤反应。CPMV 不会感染哺乳动物细胞,但作为一种危险信号,导致先天免疫细胞和随后的适应性免疫细胞的募集和激活。在本研究中,我们研究了其他二十面体病毒或植物、噬菌体和哺乳动物来源的病毒样颗粒(VLPs)是否可以类似地用作肿瘤内免疫疗法。我们的结果表明,CPMV 原位疫苗的效果优于豇豆花叶斑驳病毒(CCMV)、烟草花叶病毒(PhMV)、芝麻花叶病毒(SeMV)、噬菌体 Qβ VLP 或乙型肝炎病毒衣壳(HBVc)。此外,离体和体外检测揭示了 CPMV 的独特特性,使其成为一种更强的固有免疫刺激剂。