スマートバイオ・加藤PJにおいて、独自の抗体作製法であるCBIS法をフル稼働し、難治性がん（膵がん、悪性中皮腫、脳腫瘍、乳がん、肺がん、卵巣がん、大腸がん等）に対して迅速かつ高精度に抗体を作製中です。この度、CD44v6に対する特異的抗体が大腸がんや胃がんに対して高い抗腫瘍効果があることがCells誌に掲載されました。
Hirayama A, Tanaka T, Ohishi T, Shinoda K, Nakamura T, Nomura A, Kojo N, Araki H, Suzuki K, Kaneko MK, Suzuki H, Kato Y.
Therapeutic Potential of an Anti-CD44v6 Monoclonal Antibody in Xenograft Models of Colorectal and Gastric Cancer
Cells,14(23),1873; https://doi.org/10.3390/cells14231873, 2025 (PDF; preprint)
Abstract
CD44 variant (CD44v) isoforms are involved in promoting cancer metastasis, sustaining cancer stem cell (CSC) properties, and conferring resistance to therapeutic interventions. Consequently, the development of monoclonal antibodies (mAbs) targeting CD44v represents a crucial strategy for eliminating CD44v-positive cancer cells. Previously, an anti-CD44v6 mAb, C44Mab-9 (mouse IgG1, κ), was established. C44Mab-9 recognizes explicitly the epitope encoded by the variant exon 6-encoded region of CD44 and applies to flow cytometry, western blotting, and immunohistochemistry. To assess the therapeutic potential, a mouse IgG2a isotype of C44Mab-9 (designated C44Mab-9-mG2a) was generated, and the in vitro and in vivo antitumor activities were evaluated using gastric and colorectal cancer cell lines. C44Mab-9-mG2a demonstrated specific binding to CD44v3–10-overexpressed Chinese hamster ovary cells (CHO/CD44v3–10), as well as gastric cancer (NUGC-4) and colorectal cancer (COLO201 and COLO205) in flow cytometry. C44Mab-9-mG2a exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against CHO/CD44v3–10, NUGC-4, COLO201, and COLO205. Moreover, systemic administration of C44Mab-9-mG2a significantly inhibited tumor growth in CHO/CD44v3–10, NUGC-4, COLO201, and COLO205 xenografts compared with the control IgG2a. These findings indicate that C44Mab-9-mG2a could be applied to the mAb-based therapy against CD44v6-positive tumors.