Abstract B098: A novel monoclonal antibody for a cancer stem cell marker CD133 exerts antitumor and antimetastasis activities for colon cancers

Abstract

Abstract Background: Cancer stem cells contribute to tumorigenesis, chemoresistance, and metastasis. CD133 is a pentaspan membrane glycoprotein, and is used for the isolation of stem-like cells from cancer tissues. However, specific and sensitive monoclonal antibodies (mAbs), which are useful in every application, such flow cytometry, Western blot, and immunohistochemical analyses have not been established. Furthermore, antibody drugs targeting CD133 have not been established. Purpose: We aimed to develop novel anti-CD133 mAbs, which not only are useful for all applications but also exerts anti-tumor and anti-metastasis activities. Methods: We employed Cell-Based Immunization and Screening (CBIS) method for the development of anti-CD133 mAbs. The full-length CD133-overexpressed LN229 glioblastoma cells were immunized into mice, and flow cytometry was used for the first screening. Western blot and immunohistochemical screenings were further performed. Human colon cancer cell lines were used for examining the anti-tumor and the anti-metastasis activities of anti-CD133 mAbs. Results: We established a novel anti-CD133 mAb, CMab-43 (IgG2a, kappa), which demonstrated a sensitive and specific reaction against colon cancer cells in flow cytometry, Western blot, and immunohistochemical analyses. CMab-43 showed cancer-specific staining patterns in colon cancer tissues. Furthermore, CMab-43 significantly reduced tumor development of colon cancer cell xenografts, and inhibited experimental metastasis of colon cancer cells. Conclusion: CMab-43, which was developed by CBIS method, is useful for many applications and exerts anti-tumor or anti-metastasis activities. CMab-43 could be advantageous for antibody therapy against CD133-expressing colon cancers. Citation Format: Yukinari Kato, Tomokazu Ohishi, Manabu Kawada, Mika K Kaneko. A novel monoclonal antibody for a cancer stem cell marker CD133 exerts antitumor and antimetastasis activities for colon cancers [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B098. doi:10.1158/1535-7163.TARG-19-B098