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.KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities
Jinhyun KIM ; Jung Hee KOH ; Sung Jae CHOI ; Chan Hong JEON ; Seung-Ki KWOK ; Seong-Kyu KIM ; Chan-Bum CHOI ; Jaejoon LEE ; Changhoon LEE ; Eon Jeong NAM ; Yong-Beom PARK ; Shin-Seok LEE ; Tae-Hwan KIM ; Sung-Hwan PARK ; Jung-Yoon CHOE ; Eun-Mi KOH ; Dae-Hyun YOO ; Yeong Wook SONG ; Hyoun-Ah KIM ; Kichul SHIN
Journal of Rheumatic Diseases 2021;28(4):176-182
The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.
5.KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities
Jinhyun KIM ; Jung Hee KOH ; Sung Jae CHOI ; Chan Hong JEON ; Seung-Ki KWOK ; Seong-Kyu KIM ; Chan-Bum CHOI ; Jaejoon LEE ; Changhoon LEE ; Eon Jeong NAM ; Yong-Beom PARK ; Shin-Seok LEE ; Tae-Hwan KIM ; Sung-Hwan PARK ; Jung-Yoon CHOE ; Eun-Mi KOH ; Dae-Hyun YOO ; Yeong Wook SONG ; Hyoun-Ah KIM ; Kichul SHIN
Journal of Rheumatic Diseases 2021;28(4):176-182
The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.
6.Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus.
Eon Ju JEON ; Seong Yeon HONG ; Ji Hyun LEE
Diabetes & Metabolism Journal 2017;41(6):457-465
BACKGROUND: The aim of this study was to evaluate adipokines concentration and insulin resistance according to maternal age or obesity at pregnancy and weight change at diagnosed gestational diabetes mellitus (GDM) in pregnant women with GDM. METHODS: This study included 57 pregnant women who were diagnosed with GDM at 24 to 28 weeks of gestation. The subjects were classified into two or three groups according to pre-pregnancy body mass index (BMI, < 25 kg/m² vs. ≥25 kg/m²), maternal age at pregnancy (< 35 years old vs. ≥35 years old), and weight change during pregnancy at screening for GDM (weight change below, within, and in excess of the recommended range). They were respectively compared in each group. RESULTS: Leptin, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA2-%B were increased in the group with pre-pregnancy BMI ≥25 kg/m². Leptin and HOMA-IR were positively correlated with BMI both before pregnancy and at screening for GDM. There were no significant correlations between HOMA-IR and adipokines. HOMA-IR showed positive correlation with HOMA2-%B and negative correlation with HOMA2-%S. CONCLUSION: Leptin and HOMA-IR at diagnosed GDM were increased in the GDM patients with obesity before pregnancy. They were positively correlated with BMI both before pregnancy and at screening for GDM. The effect of maternal age at pregnancy and weight change during pregnancy at GDM screening on adipokines and insulin resistance might be less pronounced than the effect of maternal obesity.
Adipokines*
;
Body Mass Index
;
Diabetes, Gestational*
;
Female
;
Homeostasis
;
Humans
;
Insulin Resistance*
;
Insulin*
;
Leptin
;
Mass Screening
;
Maternal Age
;
Obesity
;
Pregnancy
;
Pregnant Women*
7.Tumor Regression Patterns Based on Follow-up Duration in Patients With Head and Neck Squamous Cell Carcinoma Treated With Radiotherapy or Chemoradiotherapy.
Moonkyoo KONG ; Seong Eon HONG
Clinical and Experimental Otorhinolaryngology 2015;8(4):416-421
OBJECTIVES: We describe patterns of tumor regression based on follow-up duration after radiotherapy (RT) or chemo-RT in patients with head and neck squamous cell carcinoma. METHODS: Thirty-one patients with head and neck squamous cell carcinoma were included in this study and received definitive RT or chemo-RT. The pattern of primary tumor regression after treatment was evaluated every 1 to 2 months. Predictive factors for the length of time to full regression were also analyzed. RESULTS: Among all patients, 27 patients showed regression of the primary tumor, 24 patients showed >50% regression, and 15 patients showed total regression. The primary tumor gradually regressed during the course of follow-up. The median time to full regression was 5.2 months (range, 1.3 to 17.9 months). In the 24 patients who showed >50% regression, the rate of >50% regression increased over time as follows: 25.0% at 1 month, 62.5% at 2 months, 75.0% at 3 months, 91.7% at 4 months, and 95.8% at 5 months. Higher total RT dose and shorter RT duration were associated with longer time to full regression. CONCLUSION: A substantial number of patients showed continuous regression of the primary tumor for more than 2 months after treatment. The timing for evaluation of tumor regression must be greater than 2 months from the completion of RT or chemo-RT in patients with head and neck squamous cell carcinoma.
Carcinoma, Squamous Cell*
;
Chemoradiotherapy*
;
Follow-Up Studies*
;
Head*
;
Humans
;
Neck*
;
Radiotherapy*
8.Optimal follow-up duration for evaluating objective response to radiotherapy in patients with hepatocellular carcinoma: a retrospective study.
Moonkyoo KONG ; Seong Eon HONG
Chinese Journal of Cancer 2015;34(2):79-85
The time to complete or partial (objective) response to radiotherapy in patients with hepatocellular carcinoma (HCC) is variable; thus, the reported frequency of these responses depends on the length of follow-up. However, the optimum follow-up duration is unknown. We sought to determine the optimal follow-up duration by analyzing the medical records of 25 patients with 39 HCC lesions who received definitive helical tomotherapy at a daily dose of 2 to 4 Gy at 5 fractions per week, for a total dose of 40 to 60 Gy, between January 2008 and January 2013. We determined the time to objective treatment response and local recurrence after radiotherapy and assessed several predictors of delayed treatment response. The median follow-up duration was 15.2 months (range, 7.8 to 52.1 months). Among all 39 lesions, objective responses were observed for 36 (92.3%). The median time to objective response was 3.9 months (range, 1.5 to 9.8 months). The objective response rates increased over time from 15.4% at 3 months to 71.8% at 6 months and 87.2% at 9 months. Age 60 years old or older and post-radiotherapy α-fetoprotein concentrations higher than pre-radiotherapy concentrations predicted delayed treatment response. The objective response rate continued to increase over 9 months. Therefore, to fully evaluate the treatment response of HCC, we recommend continuous observation for at least 9 months after radiotherapy.
Adult
;
Aged
;
Carcinoma, Hepatocellular
;
blood
;
radiotherapy
;
Female
;
Follow-Up Studies
;
Humans
;
Liver Neoplasms
;
blood
;
radiotherapy
;
Male
;
Middle Aged
;
Retrospective Studies
;
Treatment Outcome
;
alpha-Fetoproteins
;
analysis
9.Comparison of survival rates between patients treated with conventional radiotherapy and helical tomotherapy for head and neck cancer.
Moonkyoo KONG ; Seong Eon HONG ; Jinhyun CHOI ; Youngkyong KIM
Radiation Oncology Journal 2013;31(1):1-11
PURPOSE: Compared to conventional radiotherapy (RT), intensity-modulated radiotherapy (IMRT) significantly reduces the rate of treatment-induced late toxicities in head and neck cancer. However, a clear survival benefit of IMRT over conventional RT has not yet been shown. This study is among the first comparative study to compare the survival rates between conventional RT and helical tomotherapy in head and neck cancer. MATERIALS AND METHODS: From January 2008 to November 2011, 37 patients received conventional RT and 30 patients received helical tomotherapy for management of head and neck cancer. We retrospectively compared the survival rates between patients treated with conventional RT and helical tomotherapy, and analyzed the prognostic factors for survival. RESULTS: The 1- and 2-year locoregional recurrence-free survival rates were 61.2% and 58.1% for the conventional RT group, 89.3% and 80.3% for the helical tomotherapy group, respectively. The locoregional recurrence-free survival rates of the helical tomotherapy group were significantly higher than conventional RT group (p = 0.029). There were no significant differences in the overall and distant metastasis-free survival between the two groups. RT technique, tumor stage, and RT duration were significant prognostic factors for locoregional recurrence-free survival. CONCLUSION: This study showed the locoregional recurrence-free survival benefits of helical tomotherapy in the treatment of head and neck cancers.
Head
;
Head and Neck Neoplasms
;
Humans
;
Neck
;
Radiotherapy, Intensity-Modulated
;
Retrospective Studies
;
Survival Rate
10.Treatment Outcomes of Helical Intensity-Modulated Radiotherapy for Unresectable Hepatocellular Carcinoma.
Moonkyoo KONG ; Seong Eon HONG ; Woo Suk CHOI ; Jinhyun CHOI ; Youngkyong KIM
Gut and Liver 2013;7(3):343-351
BACKGROUND/AIMS: This study reports treatment outcomes after helical intensity-modulated radiotherapy (IMRT) in unresectable hepatocellular carcinoma (HCC) patients for whom transarterial chemoembolization (TACE) was considered ineffective or unsuitable. METHODS: From January 2008 to December 2011, 22 unresectable HCC patients received helical IMRT. A daily dose of 1.8 to 4 Gy was delivered at five fractions per week to deliver a total dose of 30 to 60 Gy. The most-prescribed dose fractionation was a total dose of 50 to 57.5 Gy, with a daily dose of 2.3 to 2.5 Gy. RESULTS: In the entire group, the objective response rate of the primary tumor was 72.7%. In the eight patients with portal vein thrombosis (PVT), the objective response rate of PVT was 50.0%. Median disease progression-free survival was 11.8 months, and the 1-year disease progression-free survival rate was 40.2%. The median overall survival was 14.4 months, and the 1- and 2-year overall survival rates were 86.4% and 69.1%, respectively. PVT and Child-Pugh classifications were significant prognostic factors for overall survival in multivariate analyses. CONCLUSIONS: Helical IMRT in patients with unresectable HCC resulted in high treatment response and survival rates. This study suggests helical IMRT is a practical treatment option for HCC patients in whom TACE is unsuitable or ineffective.
Carcinoma, Hepatocellular
;
Disease-Free Survival
;
Dose Fractionation
;
Humans
;
Portal Vein
;
Radiotherapy, Intensity-Modulated
;
Survival Rate
;
Thrombosis

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