1.Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies
Seong Min CHOI ; Ju-Hee LEE ; Soyeon KO ; Soon-Sun HONG ; Hyo-Eon JIN
Biomolecules & Therapeutics 2024;32(6):708-722
Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges.Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology;however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine.
2.Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies
Seong Min CHOI ; Ju-Hee LEE ; Soyeon KO ; Soon-Sun HONG ; Hyo-Eon JIN
Biomolecules & Therapeutics 2024;32(6):708-722
Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges.Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology;however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine.
3.Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies
Seong Min CHOI ; Ju-Hee LEE ; Soyeon KO ; Soon-Sun HONG ; Hyo-Eon JIN
Biomolecules & Therapeutics 2024;32(6):708-722
Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges.Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology;however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine.
4.Usefulness of the Rapid Antigen Test in Detecting SARS-CoV-2 for Infection Control in Hospitals
Jeong Young LEE ; Jiwon JUNG ; Jae Lim JO ; Young-Ju LIM ; Sun-Kyung KIM ; Hyejin YANG ; Soyeon PARK ; Eun Ok KIM ; Sung-Han KIM
Infection and Chemotherapy 2024;56(1):66-72
Background:
We aimed at evaluating the diagnostic performance of rapid antigen test (RAT) compared to polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 and the possible transmission of infection to close contacts from patients with negative RAT and positive PCR results.
Materials and Methods:
Patients/guardians urgently requiring admission to the ward on the same day had been hospitalized with RAT-negative result before the PCR results were available. We performed an epidemiologic investigation of the close contacts of those with negative RAT but positive PCR results after hospitalization.
Results:
A total of 4,237 RATs were performed from March to August 2022. When the PCR test was used as the reference, RAT had a sensitivity of 28.8% (17/59; 95% confidence interval [CI], 17.8 - 42.1), a specificity of 100% (4,220/4,220; 95% CI, 99.9 – 100.0), a positive predictive value of 100.0% (17/17; 95% CI, 100.0 - 100.0), and a negative predictive value of 99.0% (4,178/4,220; 95% CI, 99.3 - 99.8). The epidemiologic investigation revealed that among the 32 patients with negative RAT and subsequent positive PCR results after admission into multi-patient room, two (6.3%) showed secondary coronavirus disease 2019.
Conclusion
The secondary transmission rate from patients with negative RAT and positive PCR results was low. Our data suggest that RAT may be useful for rapid exclusion of high transmissible cases. However, further evaluation using whole genome sequencing is needed to determine the potential for transmissibility in cases showing a negative RAT but a positive PCR result
5.Korean National Healthcare-associated Infections SurveillanceSystem for Hand Hygiene Report: Data Summary from July 2019to December 2022
Sung Ran KIM ; Kyung-Sook CHA ; Oh Mee KWEON ; Mi Na KIM ; Og Son KIM ; Ji-Hee KIM ; Soyeon PARK ; Myoung Jin SHIN ; Eun-Sung YOU ; Sung Eun LEE ; Sun Ju JUNG ; Jongsuk JEOUNG ; In-Soon CHOI ; Jong Rim CHOI ; Ji-Youn CHOI ; Si-Hyeon HAN ; Hae Kyung HONG
Korean Journal of healthcare-associated Infection Control and Prevention 2024;29(1):40-47
Background:
Hand hygiene is considered the simplest and most cost-effective method of infection prevention. Regular observation and feedback on hand hygiene compliance are key strategies for its enhancement. This study evaluated the effectiveness of hand hygiene surveillance, including direct observation and feedback, by comprehensively analyzing the reported hand hygiene compliance within the Korean National Healthcare-Associated Infections Surveillance System from 2019 to 2022.
Methods:
Participating medical institutions included general hospitals and hospitals with infection control departments that consented to participate. Hand hygiene surveillance was conducted using direct observation. Collected data, including healthcare workers, clinical areas, hand hygiene moments, and hand hygiene compliance, were recorded to calculate hand hygiene compliance rates. Additionally, the volume of alcohol-based hand sanitizers used per patient per day was investigated as an indirect indicator of hand hygiene compliance. The study was conducted from July 2019 to December 2022.
Results:
Hand hygiene compliance increased from 87.2% in Q3 2019 to 89.9% in 2022. Nurses and medical technologists showed the highest compliance rates, whereas doctors showed the lowest compliance rates. Intensive care units excelled in compliance, whereas emergency de partments lagged. Compliance was highest after patient contact and lowest when the patient’s surroundings were touched. Larger hospitals consumed more alcohol-based hand sanitizers than smaller hospitals did.
Conclusion
This study confirmed an improvement in hand hygiene compliance through sustained surveillance, indicating its contribution not only to preventing infection transfer within healthcare facilities but also to fostering a culture of hand hygiene in the country.
6.Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample
Jina HAN ; Hye Jin BAEK ; Eunbi NOH ; Kyuhyun YOON ; Jung Ae KIM ; Sukhyun RYU ; Kay O LEE ; No Yai PARK ; Eunok JUNG ; Sangil KIM ; Hyukmin LEE ; Yoo-Sung HWANG ; Jaehun JUNG ; Hun Jae LEE ; Sung-il CHO ; Sangcheol OH ; Migyeong KIM ; Chang-Mo OH ; Byengchul YU ; Young-Seoub HONG ; Keonyeop KIM ; Sunjae JUNG ; Mi Ah HAN ; Moo-Sik LEE ; Jung-Jeung LEE ; Young HWANGBO ; Hyeon Woo YIM ; Yu-Mi KIM ; Joongyub LEE ; Weon-Young LEE ; Jae-Hyun PARK ; Sungsoo OH ; Heui Sug JO ; Hyeongsu KIM ; Gilwon KANG ; Hae-Sung NAM ; Ju-Hyung LEE ; Gyung-Jae OH ; Min-Ho SHIN ; Soyeon RYU ; Tae-Yoon HWANG ; Soon-Woo PARK ; Sang Kyu KIM ; Roma SEOL ; Ki-Soo PARK ; Su Young KIM ; Jun-wook KWON ; Sung Soon KIM ; Byoungguk KIM ; June-Woo LEE ; Eun Young JANG ; Ah-Ra KIM ; Jeonghyun NAM ; ; Soon Young LEE ; Dong-Hyun KIM
Epidemiology and Health 2023;45(1):e2023075-
OBJECTIVES:
We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea.
METHODS:
In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022.
RESULTS:
In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%.
CONCLUSIONS
The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.
8.Evaluation of In-Hospital Cluster of COVID-19 Associated With a Patient With Prolonged Viral Shedding Using Whole-Genome Sequencing
Jiwon JUNG ; Jungmin LEE ; Sun-Kyung KIM ; Soyeon PARK ; Young-Ju LIM ; Eun Ok KIM ; Heedo PARK ; Man-Seong PARK ; Sung-Han KIM
Journal of Korean Medical Science 2022;37(39):e289-
Background:
Patients with hematologic malignancies may produce replication-competent virus beyond 20 days of SARS-CoV-2 infection. However, data regarding the transmission of SARS-CoV-2 from patients with prolonged viral shedding is limited.
Methods:
In May 2022, four additional cases of COVID-19 were reported in a hematologic ward at a tertiary care hospital in South Korea, after an 8-week isolation of a patient with prolonged viral shedding. We performed whole-genome sequencing (WGS) of SARS-CoV-2 to evaluate the possibility of post-isolation transmission from this prolonged viral shedding.
Results:
A patient (case 1) with acute myeloid leukemia was released from isolation 54 days after the diagnosis of COVID-19 based on rising Ct value of up to 29.3, and moved to a sixpatient room. On days 10 and 11 post-isolation, his doctor (case 2) and 2 patients who were his roommates (case 3, 4) had positive SARS-CoV-2 PCR results. Additionally, 16 days postisolation, another patient (case 5) in a remote room had positive SARS-CoV-2 PCR result. All the three patients were hospitalized for ≥ 14 days when they were diagnosed with SARS-CoV-2 infection. Except for case 3, the remaining 4 cases were available for WGS, which revealed that case 1 exhibited a 7 nucleotides difference in comparison to cases 4 and 5 and case 2 displayed a 20 nucleotides difference compared with case 1, while sequences of cases 4 and 5 were identical.
Conclusions
Despite the possibility of transmission from the patient with prolonged viral shedding, no evidence of the transmission of SARS-CoV-2 from the patient with prolonged positive RT-PCR using WGS was found.
9.Rates of COVID-19 Infection Among Healthcare Workers in Designated COVID-19 Wards and General Wards
Jiwon JUNG ; Sun-Kyung KIM ; Yumi LEE ; Soyeon PARK ; Young-Ju LIM ; Eun Ok KIM ; Sung-Han KIM
Journal of Korean Medical Science 2022;37(43):e308-
Background:
To evaluate the effects of isolating coronavirus disease 2019 (COVID-19) patients in general wards, we compared the rates of COVID-19 infection in nurses and nursing assistants working in COVID-19 designated wards and in general wards of our hospital from 1 October 2021 to 21 April 2022.
Methods:
This study was conducted in a 2,700-bed tertiary care hospital in Seoul, Korea. Designated wards comprised single, negative pressure rooms and a 100% outdoor air system.
Results:
During the study period, a total of 2,698 nurses and nursing assistants were employed at our hospital, of whom 310 (11%) were working in the designated wards, and the remaining 2,388 (89%) in the general wards, and among whom 1,158 (43%) were diagnosed with COVID-19. The healthcare workers (HCWs) in the designated wards were less frequently diagnosed with COVID-19 than those in the general wards (31% vs. 45%, P < 0.001). During the period before patients with COVID-19 were isolated in general wards, and during the period after these cases were isolated in general ward, HCWs in designated wards were less frequently infected with the virus than those in general wards (7% vs. 11%, P = 0.039; and 23% vs. 33%, P < 0.001, respectively).
Conclusion
HCWs in designated wards have a lower rate of contracting COVID-19 than those in general wards. A lack of exposure to undiagnosed cases and their caregivers, greater care with social distancing outside the hospital, higher rates of 3-dose vaccinations, and the use of isolation rooms with negative pressure may be associated with this finding.
10.Interaction Effects between Individual Socioeconomic Status and Regional Deprivation on Onset of Diabetes Complication and Diabetes-Related Hospitalization among Type 2 Diabetes Patients: National Health Insurance Cohort Sample Data from 2002 to 2013
Jieun JANG ; Yeong Jun JU ; Doo Woong LEE ; Sang Ah LEE ; Sarah Soyeon OH ; Dong-Woo CHOI ; Hyeon Ji LEE ; Jaeyong SHIN
Health Policy and Management 2021;31(1):114-124
Background:
In this study, we aimed to investigate the interaction effects of individual socioeconomic status and regional deprivation on the onset of diabetes complications and diabetes-related hospitalization among type 2 diabetes patients.
Methods:
Korean National Health Insurance Service National Sample Cohort data from 2002 to 2013 were used. A total of 50,954 patients newly diagnosed with type 2 diabetes from 2004 to 2012 and aged 30 years or above were included. We classified patients into six groups according to individual income level and neighborhood deprivation: ‘high in advantaged,’ ‘high in disadvantaged,’ ‘middle in advantaged,’ ‘middle in disadvantaged,’ ‘low in advantaged,’ and ‘low in disadvantaged.’ We calculated hazard ratios (HR) of onset of diabetes complication and diabetes-related hospitalization using the Cox proportional hazard model, with the reference group as diabetes patients with high income in advantaged regions.
Results:
In terms of the interaction effects of individual income level and regional socioeconomic level, even with the same low individual income level, the group with a high regional socioeconomic level (low in advantaged) showed low HRs for the onset of diabetes complication (HR, 1.04; 95% confidence interval [CI], 1.00–1.08) compared to the ‘low in disadvantaged’ group (HR, 1.10;95% CI, 1.05–1.16). In addition, the ‘high in advantaged’ group showed slightly higher HRs for the onset of diabetes complication (HR, 1.06; 95% CI, 1.00–1.11) compared to the ‘low in advantaged’ and it appeared to be associated with slight mitigation of the risk of diabetes complication. For the low-income level, the patients in disadvantaged regions showed the highest HRs for diabetes-related hospitalization (HR, 1.29; 95% CI, 1.19–1.41) compared to the other groups.
Conclusion
Although we need to perform further investigations to reveal the mechanisms that led to our results, interaction effects individual socioeconomic status and regional deprivation might be associated with on onset of diabetes complications and diabetes-related hospitalization among type 2 diabetes patients.

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