Publications by authors named "Kazuto Shimoya"

The development of antibody drugs through animal immunization typically requires the humanization of host antibodies to address concerns about immunogenicity in humans. However, employing an animal model capable of producing human antibodies presents the opportunity to develop antibody drugs without the need for humanization. Despite the ratio of human immunoglobulin (Ig) κ to Igλ usage being approximately 60%:40%, the majority of approved antibody therapeutics are kappa antibodies, and the development of lambda antibodies as therapeutic agents has lagged behind.

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We aimed to elucidate the mechanism underlying carcinogenesis by comparing normal and BRCA1/2-mutated ovarian epithelial cells established via Sendai virus-based immortalization. Ovarian epithelial cells (normal epithelium: Ovn; with germline BRCA1 mutation: OvBRCA1; with germline BRCA2 mutation: OvBRCA2) were infected with Sendai virus vectors carrying three immortalization genes (Bmi-1, hTERT, and SV40T). The immunoreactivity to anti-epithelial cellular adhesion molecule (EpCAM) antibodies in each cell line and cells after 25 passages was confirmed using flow cytometry.

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Article Synopsis
  • - The study focused on fully human antibody-producing TC-mAb mice to generate therapeutic monoclonal antibodies (mAbs) targeting the tumor antigen, epithelial cell adhesion molecule (EpCAM).
  • - Researchers analyzed 377 mAb clones, finding that the EpCL region of EpCAM is more immunogenic than the EpRE region, confirming previous studies.
  • - They also developed a method to label mAbs with a cytotoxic agent, DM1, and demonstrated that both high-affinity and low-affinity mAbs can effectively kill colon cancer cells, highlighting the potential of TC-mAb mice for identifying candidates for antibody-drug conjugates (ADCs).
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