Citation

  • Authors: Thura, M., Al-Aidaroos, A. Q., Gupta, A., Chee, C. E., Lee, S. C., Hui, K. M., Li, J., Guan, Y. K., Yong, W. P., So, J., Chng, W. J., Ng, C. H., Zhou, J., Wang, L. Z., Yuen, J. S. P., Ho, H. S. S., Yi, S. M., Chiong, E., Choo, S. P., Ngeow, J., Ng, M. C. H., Chua, C., Yeo, E. S. A., Tan, I. B. H., Sng, J. X. E., Tan, N. Y. Z., Thiery, J. P., Goh, B. C., Zeng, Q.
  • Year: 2019
  • Journal: Nat Commun 10 2484
  • Applications: in vitro / DNA / jetPRIME
  • Cell types:
    1. Name: HCCLM3
      Description: Human hepatocellular carcinoma
      Known as: LM3 ; MHCC-LM3 ; MHCCLM3
    2. Name: Hep-53.4
      Description: Murine hepatocellular carcinoma
      Known as: HEP-53.4 ; 53.4

Method

HCCLM3: 10 µg DNA + 25 µL jetPRIME in T-75 flask

Abstract

Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3(+) cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an 'inside-out' externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcgammaII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3(+) tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy.

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