生物制药的非临床安全性测试——解决一些新出现的治疗技术的挑战

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Nonclinical safety testing of biopharmaceuticals--Addressing current challenges of these novel and emerging therapies.

Non-clinical safety testing of biopharmaceuticals can present significant challenges to human risk assessment with these often innovative and complex drugs. Hot Topics in this field were discussed recently at the 4th Annual European Biosafe General Membership meeting. In this feature article, the presentations and subsequent discussions from the main sessions are summarized. The topics covered include: (i) wanted versus unwanted immune activation, (ii) bi-specific protein scaffolds, (iii) use of Pharmacokinetic (PK)/Pharmacodynamic (PD) data to impact/optimize toxicology study design, (iv) cytokine release and challenges to human translation (v) safety testing of cell and gene therapies including chimeric antigen receptor T (CAR-T) cells and retroviral vectors and (vi) biopharmaceutical development strategies encompassing a range of diverse topics including optimizing entry of monoclonal antibodies (mAbs) into the brain, safety testing of therapeutic vaccines, non-clinical testing of biosimilars, infection in toxicology studies with immunomodulators and challenges to human risk assessment, maternal and infant anti-drug antibody (ADA) development and impact in non-human primate (NHP) developmental toxicity studies, and a summary of an NC3Rs workshop on the future vision for non-clinical safety assessment of biopharmaceuticals.

生物制药的非临床安全性测试——解决一些新出现的治疗技术的挑战       

摘要

生物制药的非临床安全性测试能够为那些新型和复杂药物对人类风险评估提出了明显的挑战。这一领域的热点话题在第四届欧洲生物安全大会上被讨论。在这篇专题文章中，将会总结这个会议中提到的观点和随之而来的讨论。这些主题包含了：1、想要的与不想要的免疫激活。2、双特异性蛋白支架。3、药代动力学（PK）/药效学（PD）数据的使用影响/优化毒理学研究设计。4、细胞因子的释放和人工翻译的挑战。5、细胞和基因治疗的安全性测试，包括嵌合抗原受体T细胞治疗技术和逆转录病毒载体的选择。6、生物制药的发展策略包含一系列不同的主题，包含单克隆抗体进入大脑的优化，治疗性疫苗的安全性测试，生物仿制药的非临床试验，免疫调节剂的毒性研究和人类风险评估的挑战，孕产妇和婴儿的抗药物抗体（艾达）在非人类的灵长类动物的发展和影响（NHP）以及发育毒性的研究，以及一个nc3rs专题的综述。