双特异性抗体研究进展

抗体药物具有特异性高、不良反应少的特点，已成为肿瘤治疗的热点。双特异性抗体（双抗）是指同时结合2个不同抗原或同一抗原2个表位的抗体。与单特异性抗体相比，双抗具有高度特异性，增强了治疗有效性和安全性，同时减少了不良反应。已有多种双抗药物获批上市，进入临床研究的双抗药物数量不断增加。双抗药物的形式持续在更新，应用范围也在扩大，在未来具有非常好的应用前景。此文就目前已有的双抗类型、作用机制及目前双抗制备上面临的困难等进行概述。     

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection

BackgroundWe assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection.MethodsAmong 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay.ResultsHBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001.ConclusionHBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.     

抗PD-1/PD-L1免疫检查点抑制剂的皮肤免疫相关不良反应的研究进展

随着免疫检查点抑制剂（immune checkpoint inhibitors，ICPI）在国内外临床试验和应用中的逐步推广，越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1（programmed death-1，PD-1）及其配体（PD-1 ligand，PD-L1）免疫检查点抑制剂已被美国食品药品管理局（FDA）批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应，皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。     

An update on epidemiology,diagnosis & management of NMO-SD in the tertiary neurology department of Marrakech (Morocco)

IntroductionNeuromyelitis optica (NMO) and NMO spectrum disorders (NMO-SD) are inflammatory demyelinating diseases of the central nervous system. There are few epidemiological studies devoted to NMO, especially in Africa and the Middle East, but individual cases and series have been reported from many countries across the African continent.ObjectivesTo describe the epidemiology, diagnosis, and management of NMO patients followed at the Mohammed VI University Hospital of Marrakech.Patients and methodsThis was a hospital-based retrospective study of 52 patients with NMO diagnosed and followed at the Neurology department of the University Hospital of Marrakech from 2004 to July 2019. The 2006 diagnostic criteria of NMOSD were used for patients admitted before 2015 for inflammatory disease of the central nervous system and the 2015 diagnostic criteria of NMO-SD for all patients thereafter. Collected data were analysed using SPSS software.ResultsThe study concerned 52 patients, 18 males and 34 females. Median age at disease onset was 32.5 years (range 7–55). Mean time between symptom onset and diagnosis of NMO was nine months 18 days (range 7 days to 4 years). In most patients, manifestations included visual acuity, tetraparesis, and sensorial disorders. Refractory vomiting and hiccup were noted in the first attack in 19% of patients. Two patients had hypersomnia and polyphagia, and one had been treated for depression ten months before the development of severe tetraplegia. Magnetic resonance imaging did not show any brain lesions in 29% of patients. Cervical myelitis extending to more than three vertebrae was found in 60% of patients. AQP4-antibody assay was performed only in 57.7% of patients, and was positive in 38.4%; anti-MOG was positive in four anti-AQP4 seronegative patients. Management strategies for NMO-SD included methylprednisolone pulses (70% of patients), plasmapheresis (25%), and rituximab (since 2017) for 46%. Outcome was favourable in 40% of patients and has remained stable in 50% of them.ConclusionAnti-NMO assays, made available during the last five years with the help of The Guthy-Jackson Charitable Foundation, have led to a clear jump in the number of cases diagnosed. Major advances in the field of epidemiology, imaging, and pathophysiology of NMO-SD have led to improved patient care and outcome.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron

1. Download : Download high-res image (182KB)
2. Download : Download full-size image