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| 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 | STBC MIMOOFDM peak-to-average power ratio reduction by cross-antenna rotation and inversion 显示文摘 | TAN M Z LATINOVIC Z BAR-NESS Y | 2005 | IEEE Communications Letters2005，9，7： | 1 |
| 3 | No Association Between Immunization and Guillain-Barre syndrome in the United Kingdom, 1992 to 2000 显示文摘 | Hughes RA Charhon J Latinovic R | 2006 | Arch InterMed2006，166，12： | 1 |
| 4 | Sudden infant death syndrome and maternal depression显示文摘 | Howard L M Kirkwood G Latinovic R | 2007 | Journal of Clinical Psychiatry2007，68，8： | 1 |
| 5 | Physical and psychological comorbidity in irritable bowel syndrome:a matched cohort study using the general practice research database显示文摘 | Jones R Latinovic R Charlton J | 2006 | Aliment Pharmacol Ther2006，24，5： | 1 |
| 6 | Incidence of common compressive neuropathies in primary care 显示文摘 | Latinovic R Gulliford MC Hughes RA | 2006 | J Neurol Neuresurg Psychiatry2006，77，2： | 1 |
| 7 | Research on air pressure drop in helically-finned tube heat exchangers显示文摘 | Genic S B Jacimovic B M Latinovic B R | 2006 | Applied Thermal Engineering2006，26，56： | 1 |
| 8 | STBC MIMO-OFDM peak to average power ratio reduction by cross antenna rotation and inversion显示文摘 | Tan M Latinovic Z Bar-Ness Y | 2005 | IEEE Gommu Lett2005，9，7： | 1 |
| 9 | STBC MIMO-OFDM Peak-to-Average Power Ratio Reduction by Cross-Antenna Rotation and Inversion 显示文摘 | Tan M Latinovic Z Bar-Ness Y | 2005 | 1EEE Communications Let- ters2005，9，7： | 1 |
| 10 | Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1 显示文摘 | Heredia A Latinovic O Gallo RC | 2008 | Proc Nat Acad Sci USA2008，105，20： | 1 |
| 11 | 玻璃体腔注射贝伐单抗治疗PDR黄斑水肿后患者的满意度和视力(英文)显示文摘目的:增生性糖尿病性视网膜病播散性视网膜激光光凝后,用非选择性抗VEGF抑制剂贝伐单抗治疗糖尿病性黄斑水肿,调查患者自我评估的视功能及视力。方法:30例30眼增生性糖尿病性视网膜病伴持续性糖尿病性黄斑水肿连续病例,播散性视网膜激光光凝后,1.25mg贝伐单抗0.05mL (Avastin)单剂量玻璃体腔注射治疗。对照组包括30例30眼增生性糖尿病性视网膜病,只接受播散性视网膜激光光凝。主要的调查结果包括Snellen视力,眼底临床检查和患者自我用0-100分数值范围评价的视觉质量。结果:贝伐单抗组的平均基线视力为0.48±0.58 logMAR,对照组为0.61±0.78 (两组无显著差异)。6mo后,视力没有显著的变化,贝伐单抗组和对照组分别为0.33±0.41和0.52±0.68。临床检查显示黄斑水肿仅有一些改善趋势。患者用直观模拟标度尺主观评价视功能结果显示注射贝伐单抗6mo后由60.2±17.5改善至76.0±15.6 (P<0.001)。对照组自我评估视功能平均值为59.6±19.8,与贝伐单抗组基线值无显著差异,但是低于注射贝伐单抗后分数,差异有高度显著性(P<0.01)。结论:治疗增生性糖尿病性视网膜病的黄斑水肿,贝伐单抗(Avastin)玻璃体腔注射作为播散性激光光凝的辅助治疗较单纯的激光治疗后患者满意度和自我评价的视力显著改善。患者视力在6mo后无明显变化。 | Lala Ceklic Slobodanka Latinovic Aljoscha S Neubauer Marijana Malesevic | 2009 | 国际眼科杂志2009，9，9： | 1 |
| 12 | STBC MIMO-OFDM peak-to-average power ratio reduction by cross-antenna rotation and inversion显示文摘 | TAN M Z LATINOVIC Z YEHESKEL B N | 2005 | Communications Letters2005，9，7： | 1 |
| 13 | Incidence of com- mon compressive neuropathies in primary care显示文摘 | Latinovic R Gulliford MC Hughes RA | 2006 | Neu- rol Neurosurg Psychiatry2006，77，： | 1 |
| 14 | SFBC MIMO-OFDM Peak-to-average Power Ratio Reduction by Polyphase Interleaving and Inversion 显示文摘 | Latinovic Z Bar-Ness Y | 2006 | IEEE Communications Letters2006，10，4： | 1 |
| 15 | A new approach to detection of defects in rolling element bear- ings based on statistical pattern recognition显示文摘 | STEPANIC P LATINOVIC L V DJUROVIC Z | 2009 | Int J Adv Manuf Technol2009，45，： | 1 |
| 16 | 初级护理中心的常见压迫性神经病变发病率显示文摘Apart from carpal tunnel syndrome, there are no population based studies of the epidemiology of compressive neuropathies. To provide this information, new presentations of compressive neuropathies among patients registered with 253 general practices in the UK General Practice Research Database with 1.83 million patient years at risk in 2000 were analysed. The study revealed that in 2000 the annual age standardised rates per 100 000 of new presentations in primary care were: carpal tunnel syndrome, men 87.8/women 192.8; Morton’s metatarsalgia, men 50.2/women 87.5; ulnar neuropathy, men 25.2/women 18.9; meralgia paraesthetica, men 10.7/women 13.2; and radial neuropathy, men 2.97/women 1.42. New presentations were most frequent at ages 55-64 years except for carpal tunnel syndrome, which was most frequent in women aged 45-54 years, and radial nerve palsy, which was most frequent in men aged 75-84 years. In 2000, operative treatment was undertaken for 31%of new presentations of carpal tunnel syndrome, 3%of Morton’s metatarsalgia, and 30%of ulnar neuropathy. | Latinovic R. Gulliford M. C. Hughes R. A. C. 陈孝东(译) | 2006 | 世界核心医学期刊文摘(神经病学分册)2006，2，6： | 1 |
| 17 | STBC MIMO-OFDM peak-to-average power ratio reduction by cross-antenna rotation and inversion 显示文摘 | Tan M Latinovic Z Yeheskel B N | 2005 | IEEE Communication Letters2005，9，7： | 1 |
| 18 | Research on the air pressure drop in plate finned tube heat exchangers显示文摘 | JACIMOVIC B M GENIC S B LATINOVIC B R | 2006 | International Journal of Refrigeration2006，29，： | 1 |
| 19 | Imaging single retrovirus entry through alternative receptor isoforms and intermediates of virus-endosome fusion显示文摘 | Jha N K Latinovic O Martin E | 2011 | PLoS Pathogens2011，7，1： | 1 |
| 20 | Optimal design of BTA deep-hole cutting tools with staggered cutters 显示文摘 | V N Latinovic M O M Osman | 2001 | Journal of Manufacturing Science and Engineering2001，27，1： | 1 |
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