Characterization of human anti-EpCAM antibodies for developing an antibody-drug conjugate.

We previously generated fully human antibody-producing TC-mAb mice for obtaining potential therapeutic monoclonal antibodies (mAbs). In this study, we investigated 377 clones of fully human mAbs against a tumor antigen, epithelial cell adhesion molecule (EpCAM), to determine their antigen binding properties. We revealed that a wide variety of mAbs against EpCAM can be obtained from TC-mAb mice by the combination of epitope mapping analysis of mAbs to EpCAM and native conformational recognition analysis. Analysis of 72 mAbs reacting with the native form of EpCAM indicated that the EpCL region (amino acids 24-80) is more antigenic than the EpRE region (81-265), consistent with numerous previous studies. To evaluate the potential of mAbs against antibody-drug conjugates, mAbs were directly labeled with DM1, a maytansine derivative, using an affinity peptide-based chemical conjugation (CCAP) method. The cytotoxicity of the conjugates against a human colon cancer cell line could be clearly detected with high-affinity as well as low-affinity mAbs by the CCAP method, suggesting the advantage of this method. Thus, this study demonstrated that TC-mAb mice can provide a wide variety of antibodies and revealed an effective way of identifying candidates for fully human ADC therapeutics.

Engineering of human induced pluripotent stem cells via human artificial chromosome vectors for cell therapy and disease modeling.

Genetic engineering of induced pluripotent stem cells (iPSCs) holds great promise for gene and cell therapy as well as drug discovery. However, there are potential concerns regarding the safety and control of gene expression using conventional vectors such as viruses and plasmids. Although human artificial chromosome (HAC) vectors have several advantages as a gene delivery vector, including stable episomal maintenance and the ability to carry large gene inserts, the full potential of HAC transfer into iPSCs still needs to be explored. Here, we provide evidence of a HAC transfer into human iPSCs by microcell-mediated chromosome transfer via measles virus envelope proteins for various applications, including gene and cell therapy, establishment of versatile human iPSCs capable of gene loading and differentiation into T cells, and disease modeling for aneuploidy syndrome. Thus, engineering of human iPSCs via desired HAC vectors is expected to be widely applied in biomedical research.

Evaluation of endoscopic and histological findings in Helicobacter pylori-positive Japanese young adults.

BACKGROUND AND AIM: Many studies have shown that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers and gastric carcinoma in adults. However, little is known about these associations in the younger population. The aim of this study was to clarify endoscopic and histological findings in H. pylori-positive young adults. METHODS: Two hundred consecutive outpatients younger than 29 years old undergoing esophago-gastroduodenal endoscopy at four hospitals between 2001 and 2002 were eligible for this study. At endoscopy, three biopsy specimens were obtained from the mid-antrum, the angulus and the mid-corpus. Endoscopic and histological interpretations were based on the updated Sydney System. H. pylori infection was determined by histology and serology. RESULTS: The rates of H. pylori infection were 1.2% (1/86) in normal, 95.8% (46/48) in gastritis, 97.8% (45/46) in duodenal ulcers, 100% (17/17) in gastric ulcers, and 100% (3/3) in gastric carcinomas. Endoscopic findings in 112 H. pylori-positive patients were 25 normal (22.3%), 38 atrophy (33.9%), 18 erosion (16.1%), and 31 nodularity (27.7%). Histological findings of H. pylori-positive patients in the anturm revealed mononuclear cell and neutrophil infiltration in 100%, and atrophy in 27.7%. Histological findings of H. pylori-positive patients in the corpus revealed mononuclear cell infiltration in 75%, neutrophil infiltration in 60.7%, and atrophy in 28.6%. CONCLUSIONS: The study shows that H. pylori infection is strongly associated with chronic gastritis and peptic ulcers, and that histological corpus gastritis was found with high frequency in Japanese young adults.