It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.
Management of primary liver abscess caused by K. pneumoniae with use of first-generation cephalosporins and percutaneous drainage was associated with low rates of mortality, metastatic infection, and complications. These rates are comparable to those reported for third-generation cephalosporins.
The most common cause of eosinophilic meningitis is the rat lungworm Angiostrongylus cantonensis a parasite that is endemic in the southeast Asian and Pacific regions. Outbreaks of eosinophilic meningitis associated with drinking raw vegetable juice are rarely reported, even in regions of endemic infection. We performed a cohort study among Taiwanese with eosinophilic meningitis who drank raw vegetable juice within three months of the onset of the outbreak. Clinical manifestations, laboratory examinations, and outcomes were prospectively followed. Five native Taiwanese met the case definition of eosinophilic meningitis. Specific antibodies to A. cantonensis were detected in the serum of five of the patients and in the cerebrospinal fluid (CSF) of four of the patients. Central nervous system manifestations included headache (n = 5 [100%]), Brudzinski's sign/stiff neck (n = 5 [100%]), hyperesthesia/paresthesias (n = 5 [100%]), and cranial nerve palsy (n = 1 [20%]). Laboratory findings included peripheral (n = 5 [100%]) and CSF eosinophilia (n = 4 [80%]), transient increases in the white blood cell count (n = 1 [20%]), and in serum levels of creatine kinase (n = 1 [20%]). Meningeal enhancement, as well as high signal intensity, at the subcortical white matter on T2 weighted and fluid attenuated inversion recovery images were observed on magnetic resonance imaging in four patients. There were three episodes of relapse during treatment and all resolved with after a lumbar puncture and/or administration of steroids. At the 12-month follow up, all five patients had recovered without neurologic sequelae. Risk factors identification showed that consumption of raw vegetable juice was associated with illness (Pearson correlation test r = 0.867, P = 0.01). There was association between the presence of raw vegetable juice and CSF eosinophilia (Spearman's correlation test r = 0.816, P = 0.004).
Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Human infection occurs after ingestion of the worms in raw snails or fish that serve as intermediate hosts. Two outbreaks of central nervous system infection with A. cantonensis occurred in Kaoshiung, Taiwan, during 1998 and 1999 among Thai laborers who ate raw snails. A detailed clinical studies of 17 of these patients was conducted, including study of 13 patients who underwent magnetic resonance imaging (MRI) scans of the brain. The MRI scans revealed high signal intensities over the globus pallidus and cerebral peduncle on TI-weighted imaging, leptomeningeal enhancement, ventriculomegaly, and punctate areas of abnormal enhancement within the cerebral and cerebellar hemisphere on gadolinium-enhancing T1 imaging, and a hyperintense signal on T2-weighted images. There was a significant correlation between severity of headache, cerebrospinal fluid (CSF) pleocytosis, and CSF and blood eosinophilia with MRI signal intensity in T1-weighted imaging (P < 0.05). Eosinophilic meningitis produced by A. cantonensis needs to added to the list of causes of hyperintense basal ganglia lesions found on T1-weighted MRI scans in tropical countries.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.