|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy显示文摘It remains unclear why the clinically used anti-CTLA-4 antibodies, popularly called checkpoint inhibitors, have severe immunotherapy-related adverse effects (irAEs) and yet suboptimal cancer immunotherapeutic effects (CITE). Here we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface by the LRBA-dependent mechanism. Disrupting CTLA-4 recycling results in robust CTLA-4 downregulation by all anti-CTLA-4 antibodies and confers toxicity to a non-irAE-prone anti-CTLA-4 mAb. Conversely, increasing the pH sensitivity of TremeIgG1 by introducing designed tyrosine-to-histidine mutations prevents antibody-triggered lysosomal CTLA-4 downregulation and dramatically attenuates irAE. Surprisingly, by avoiding CTLA-4 downregulation and due to their increased bioavailability, pH-sensitive anti-CTLA-4 antibodies are more effective in intratumor regulatory T-cell depletion and rejection of large established tumors. Our data establish a new paradigm for cancer research that allows for abrogating irAE while increasing CITE of anti-CTLA-4 antibodies. | Yan Zhang Xuexiang Du Mingyue Liu Fei Tang Peng Zhang Chunxia Ai James K. Fields Eric J. Sundberg Olga S. Latinovic Martin Devenport Pan Zheng Yang Liu | 2019 | Cell Research2019，29，8： | 6 |
| 2 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock 显示文摘 | Carcillo :IA Fields AI | 2002 | Crit Care Med2002，30，6： | 1 |
| 3 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patient in septic shock 显示文摘 | Carcillo JA Fields AI | 2002 | Crit Care Med2002，30，6： | 1 |
| 4 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carillo JA Fields AI | 2002 | Crit Care Med2002，30，6： | 1 |
| 5 | Sequential cardiopulmonary variables of infants and children in septic shock 显示文摘 | Pollack MM Fields AI Ruttimann UE | 1984 | Grit Care Med1984，12，7： | 1 |
| 6 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carcillo JA Fields AI | 2002 | Crit Care Med2002，30，6： | 1 |
| 7 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock 显示文摘 | Carcillo JA Fields AI Comite de Forca-Tarefa | 2002 | J Pediatr (Rio J)2002，78，6： | 1 |
| 8 | Endogenous pain control systems: Brainstem spinal pathways and endorphin circuitry 显示文摘 | Basbaum AI Fields HL | 1984 | Annu Rev Neurosci1984，7，： | 1 |
| 9 | Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns 显示文摘 | Jellison BJ Field AS Medow J et ai | 2004 | AJNR2004，25，3： | 1 |
| 10 | Clinical practice parameters for homodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carcillo JA Fields AI Task Force Committee Members | 2002 | Crit Care Med2002，30，： | 1 |
| 11 | Clinical practice parame- ters for hemodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carcillo JA Fields AI American College of Critical Care Medi- cine Task Force Committee Members | 2002 | Crit CareMed2002，30，6： | 1 |
| 12 | Endogenous pain control system:brainstem spinal pathways and endorphin circuitry显示文摘 | Fields HL | 1984 | Annu Rev Neurosci1984，7，1： | 1 |
| 13 | Clinical practice parameters for bemodynamic support of pediatric and neonatal patients in septic shock 显示文摘 | Carcillo JA Field AI Task Force Committee Members | 2002 | Crit Care Med2002，30，6： | 1 |
| 14 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carcillo JA Field AI Task Force Committee Members | 2002 | Crit Care Med2002，30，6： | 1 |
| 15 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carcillo JA Fields AI | 2002 | J Pediatr2002，78，6： | 1 |
| 16 | Effects of depression and Parkinson's disease on cognitive functioning显示文摘 | Norman S Troster AI Fields JA | 2002 | J Neuro- psychiatry Clin Neurosci2002，14，1： | 1 |
| 17 | Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock显示文摘 | Carcillo JA Fields AI Task Force Committee Members | 2002 | Crit Care Med2002，30，6： | 1 |
| 18 | Peptides and the primary affer- ent nociceptor显示文摘 | Levhle JD Fields HL Basbaum AI | 1993 | J Neurosci1993，13，6： | 1 |
| 19 | Neuropsychological sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a critical review显示文摘 | Woods SP Fields JA Troster AI | 2002 | Neuropsychol Rev2002，12，2： | 1 |
| 20 | Effects of depression and Parkinson's disease on cognitive functioning显示文摘 | Norman S Troster AI Fields JA | 2002 | J Neuropsychiatry Clin Neurolsci2002，14，1： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员