PDF(Pubmed)
Abstract：
The use of immune checkpoint inhibitors, which activate T cells, is a paradigm shift in the treatment of non-small cell lung cancer. However, the overall response remains low. To address this limitation, here we describe a novel platform, termed antibody-conjugated drug-loaded nanotherapeutics (ADN), which combines immunotherapy and molecularly targeted therapy. An ADN was designed with an anti-CD47 and anti-programmed death ligand 1 (PDL1) antibody pair on the surface of the nanoparticle and a molecularly targeted inhibitor of the PI3K (phosphatidylinositol 3-kinase)/AKT/mTOR (mammalian target of rapamycin) pathway, PI103, entrapped in the nanoparticle. The anti-CD47-PDL1-ADN exhibited greater antitumor efficacy than current treatment options with a PDL1 inhibitor in vivo in an aggressive lung cancer immunocompetent mouse model. Dual antibody-drug-loaded nanotherapeutics can emerge as an attractive platform to improve outcomes with cancer immunotherapy.
摘要：
使用免疫检查点抑制剂，激活T细胞，是非小细胞肺癌治疗的范式转变。然而,总体反应仍然很低。为了解决这个限制，在这里我们描述一个新颖的平台，称为抗体缀合的载药纳米治疗剂（ADN），结合了免疫治疗和分子靶向治疗。设计了一种ADN，在纳米颗粒表面上具有抗CD47和抗程序性死亡配体1（PDL1）抗体对和PI3K（磷脂酰肌醇3-激酶）/AKT/mTOR（哺乳动物雷帕霉素靶标）途径的分子靶向抑制剂，PI103,包埋在纳米颗粒中。在侵袭性肺癌免疫活性小鼠模型中,抗CD47-PDL1-ADN表现出比使用PDL1抑制剂的当前治疗选择更大的抗肿瘤功效。双重抗体-药物负载的纳米治疗剂可以成为改善癌症免疫治疗结果的有吸引力的平台。
