Trends of Mammography Use in a National Breast Cancer Screening Program, 2004-2008

Purpose: Korea started breast cancer screening as part of the National Cancer Screening Program (NCSP) in 1999. In order to identify under-served groups, we investigated mammography uptake in the National Breast Cancer Screening Program. Materials and Methods: The study population was participants in the National Breast Cancer Screening Program from 2004 to 2008. We analyzed participation rates by insurance type, age group, and area of residence. Results: Total participation rates for breast cancer screening increased from 18.2% in 2004 to 35.0% in 2008. The participation rate in the group aged 60 to 69 years showed the greatest increase, 21.3%, among the four age groups. Although the screening rate increased continuously, the participation rate of the Medical Aid Program (MAP) group was low compared to the National Health Insurance (NHI) group. Moreover, the increasing trend of mammography uptake in the MAP group was much lower than that of the NHI group. Conclusion: The participation rate for breast cancer screening in the NCSP in Korea has increased. However, the participation rate in mammography among MAP recipients is still lower than that of NHI beneficiaries. To increase mammography uptake, it is important to make it available to everyone by ensuring inclusion of all population subgroups.ope

Results of Colorectal Cancer Screening of the National Cancer Screening Program in Korea, 2008

PURPOSE: This study aims to investigate the current situation of national colorectal cancer screening by analyzing participation rates, positive rates of screening methods and screening rate of secondary screening tests in colorectal screening of the national cancer screening program in 2008.0aMATERIALS AND METHODS: With database about target population and screened individuals of the national cancer screening program, the results of target population and participants of colorectal cancer screening in 2008 were analyzed. Among adults aged over 50 years of medical aid and beneficiaries of national health insurance paying lower 50% premiums in the total subscribers, 4,640,365 were target population of colorectal cancer screening and the data of 984,915 undergoing fecal occult blood test (FOBT) as a primary screening were analyzed.0aRESULTS: The colorectal cancer screening rate was 21.2% and the rates of national health insurance subscribers, females and the elderly aged 60-64 years were higher than those of others. The recipients with a positive result in FOBT recorded approximately 7.5%. Medical aid beneficiaries (7.9%), males (8.8%) and seniors aged over 75 years (9.1%) showed higher positive rates than the average one. Out of the FOBT positive recipients, 43.0% took a secondary screening and the rate undergoing colonoscopy (31.4%) was higher than that of doing double-contrast barium enema test (11.6%).0aCONCLUSION: Colorectal cancer screening rate of medical aid beneficiaries and people paying lower 50% premiums among national health insurance subscribers, was different according to demographic characters (gender, age and types of health insurance). This finding meant that screening for the vulnerable needed to be encouraged by considering socio-demographic characters. Additionally, more efforts were necessary to increase the secondary screening rate of people with a positive result in primary one.ope

In-Orbit Results and Attitude Analysis of the SNUGLITE Cube-Satellite

SNUGLITE (Seoul National University Global navigation satellite system Laboratory satellITE) is a two-unit cube satellite (CubeSat) with dimensions 10 × 10 × 23 cm that requires an attitude system for missions and ground station telecommunication. A linear-quadratic-Gaussian-based optimal attitude system for the CubeSat platform has been developed using low-cost sensors, with the in-orbit verification of the attitude system being is one of main study objectives. Since launch, the SNUGLITE CubeSat has continuously broadcast in-orbit status information. In this study, a methodology for the analysis of in-orbit attitude estimation results using received data is presented, and this was achieved by comparing two sun-pointing vectors, i.e., the sun-pointing vector calculated using estimated attitude with the positions of the sun and the satellite and the reference vector generated by the power levels of the solar panels. Because the satellite position was required for the attitude analysis, the verification of the performance of the own-developed on-board Global Positioning System (GPS) receiver is also briefly described. Analyses indicate that the attitude estimation of the SNUGLITE CubeSat has achieved an in-orbit real-time pointing accuracy with a root mean square of 6.1°

Development of anti-CD32b antibodies with enhanced Fc function for the treatment of B and plasma cell malignancies

The sole inhibitory Fcγ receptor CD32b (FcγR2b) is expressed throughout B and plasma cell development and on their malignant counterparts with the highest expression found on multiple myeloma. Additionally, CD32b expression on tumor cells is known to sequester IgG Fc whereby providing a mechanism of resistance to therapeutic monoclonal antibodies (mAb) with Fc dependent activity. Taken together, CD32b represents an attractive tumor antigen for targeting with a mAb. To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. The complementarity-determining regions (CDRs) of these antibodies bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcR on immune effector cells. NVS32b mAbs selectively depletes CD32b+ healthy and malignant B cells but spares myeloid cells and CD32a+ cells. These antibodies mediate potent killing of opsonized cells via antibody dependent cellular cytotoxicity and phagocytosis (ADCC & ADCP), as well as complement dependent cytotoxicity (CDC). Additionally, NVS32b CDRs block the CD32b Fc binding domain, thereby minimizing CD32b mediated resistance to therapeutic mAbs with Fc dependent activity, including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b positive xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor microenvironment and enhancement of DC maturation in response to immune-complexes. The activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed on samples from CLL and MM patients. NVS32b mAbs demonstrated great therapeutic potential, as a single agent or in combination with other mAb therapeutics

Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies

The sole inhibitory Fcγ receptor CD32b (FcγR2b) is expressed throughout B and plasma cell development and on their malignant counterparts with the highest expression found on multiple myeloma. Additionally, CD32b expression on tumor cells is known to sequester IgG Fc whereby providing a mechanism of resistance to therapeutic monoclonal antibodies (mAb) with Fc dependent activity. Taken together, CD32b represents an attractive tumor antigen for targeting with a mAb. To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. The complementarity-determining regions (CDRs) of these antibodies bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcR on immune effector cells. NVS32b mAbs selectively depletes CD32b+ healthy and malignant B cells but spares myeloid cells and CD32a+ cells. These antibodies mediate potent killing of opsonized cells via antibody dependent cellular cytotoxicity and phagocytosis (ADCC & ADCP), as well as complement dependent cytotoxicity (CDC). Additionally, NVS32b CDRs block the CD32b Fc binding domain, thereby minimizing CD32b mediated resistance to therapeutic mAbs with Fc dependent activity, including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b positive xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor microenvironment and enhancement of DC maturation in response to immune-complexes. The activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed on samples from CLL and MM patients. NVS32b mAbs demonstrated great therapeutic potential, as a single agent or in combination with other mAb therapeutics

Development of anti-CD32b antibodies with enhanced Fc function for the treatment of B and plasma cell malignancies

The sole inhibitory Fcg receptor CD32b (Fcg RIIb) is expressed throughout B and plasma cell development and on their malignant counterparts. CD32b expression on malignant B cells is known to provide a mechanism of resistance to rituximab that can be ameliorated with a CD32b-blocking antibody. CD32b, therefore, represents an attractive tumor antigen for targeting with a monoclonal antibody (mAb). To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. Their complementarity-determining regions (CDR) bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of Fcg RIIIa on immune effector cells. The NVS32b mAbs selectively target CD32bþ malignant cells and healthy B cells but not myeloid cells. They mediate potent killing of opsonized CD32bþ cells via antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) as well as complement-dependent cytotoxicity (CDC). In addition, NVS32b CDRs block the CD32b Fc–binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32bþ xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor and enhancement of dendritic cell maturation in response to immune complexes. Finally, the activity of NVS32b mAbs on CD32bþ primary malignant B and plasma cells was confirmed using samples from patients with B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32bþ malignant cells

Discovery and optimization of HKT288, a cadherin-6-targeting ADC for the treatment of ovarian and renal cancers

Despite an improving therapeutic landscape, significant challenges remain in treating the majority of patients with advanced ovarian or renal cancer. We identified the cell-cell adhesion molecule cadherin-6 (CDH6) as a lineage gene having significant differential expression in ovarian and kidney cancers. HKT288 is an optimized CDH6-targeting DM4-based antibody-drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance of linker choice for optimal antitumor activity and highlights CDH6 as an antigen for biotherapeutic development. To more robustly predict patient benefit of targeting CDH6, we incorporate a population-based patient-derived xenograft (PDX) clinical trial (PCT) to capture the heterogeneity of response across an unselected cohort of 30 models-a novel preclinical approach in ADC development. HKT288 induces durable tumor regressions of ovarian and renal cancer models in vivo, including 40% of models on the PCT, and features a preclinical safety profile supportive of progression toward clinical evaluation. SIGNIFICANCE: We identify CDH6 as a target for biotherapeutics development and demonstrate how an integrated pharmacology strategy that incorporates mechanistic pharmacodynamics and toxicology studies provides a rich dataset for optimizing the therapeutic format. We highlight how a populationbased PDX clinical trial and retrospective biomarker analysis can provide correlates of activity and response to guide initial patient selection for fi rst-in-human trials of HKT288