Hasani-Sadrabadi Mohammad Mahdi, Majedi Fatemeh S, Miller Matthew L, Thauland Timothy J, Bouchard Louis-S, Li Song, Butte Manish J
Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA.
Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095 USA.
Mater Horiz. 2020 Nov 1;7(11):3028-3033. doi: 10.1039/d0mh00755b. Epub 2020 Sep 29.
Recent innovations in immunoregulatory treatments have demonstrated both the impressive potential and vital role of T cells in fighting cancer. These treatments come at a cost, with systemic side effects including life-threatening autoimmunity and immune dysregulation the norm. Here, we developed an approach to locally synthesize immune therapies and in this way, avoid systemic toxicity. Rather than just encapsulating cytokines, we endowed our nanoparticles with transcriptional and translational machinery to cytokines locally, , and on demand (activated by light). We demonstrated the capabilities of these particles and , in a mouse model of melanoma, and showed that tumor-infiltrating T cells were more highly activated in the context of these "microfactory" particles that make the synthetic cytokine.
免疫调节治疗领域的最新创新成果彰显了T细胞在对抗癌症方面令人瞩目的潜力和至关重要的作用。这些治疗方法存在一定代价,全身性副作用包括危及生命的自身免疫和免疫失调是常见现象。在此,我们开发了一种局部合成免疫疗法的方法,以此避免全身毒性。我们的纳米颗粒并非仅仅包裹细胞因子,而是配备了转录和翻译机制,能够根据需要(通过光激活)在局部合成细胞因子。我们在黑色素瘤小鼠模型中展示了这些颗粒的功能,并表明在这些能够合成细胞因子的“微型工厂”颗粒环境中,肿瘤浸润T细胞的激活程度更高。