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Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

Cellular & Molecular Immunology volume 8, pages 157–163 (2011)Cite this article

Abstract

Many monoclonal antibodies (mAbs) have been extensively used in the clinic, such as rituximab to treat lymphoma. However, resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy. Complement is one of the main mediators of antibody-based cancer therapy via the complement-dependent cytolysis (CDC) effect. CD59 plays a critical role in resistance to mAbs through the CDC effect. In this paper, we attempted to investigate whether the novel CD59 inhibitor, recombinant ILYd4, was effective in enhancing the rituximab-mediated CDC effect on rituximab-sensitive RL-7 lymphoma cells and rituximab-induced resistant RR51.2 cells. Meanwhile, the CDC effects, which were mediated by rituximab and anti-CD24 mAb, on the refractory multiple myeloma (MM) cell line ARH-77 and the solid tumor osteosarcoma cell line Saos-2, were respectively investigated. We found that rILYd4 rendered the refractory cells sensitive to the mAb-mediated CDC effect and that rILYd4 exhibited a synergistic effect with the mAb that resulted in tumor cells lysis. This effect on tumor cell lysis was apparent on both hematological tumors and solid tumors. Therefore, rILYd4 may serve as an adjuvant for mAb mediated-tumor immunotherapy.

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Acknowledgements

This work was supported by the US NIH through grant RO1 AI061174 (XBQ) and grant R21 CA141324 (XBQ), the Harvard Technology Development Accelerator Fund (XBQ), and the Fund of the China Scholarship Council No. 2008638052 (TY). We are grateful to Ms Annie Qin, a Harvard University undergraduate student, for helpful editorial assistance.

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Authors and Affiliations

  1. Department of Musculoskeletal Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Tao You & Jingnan Shen

  2. Laboratory for Translational Research, Harvard Medical School, Cambridge, MA, USA

    Tao You, Weiguo Hu, Xiaowen Ge & Xuebin Qin

  3. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    Tao You, Weiguo Hu & Xuebin Qin

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Correspondence to Xuebin Qin.

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You, T., Hu, W., Ge, X. et al. Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells. Cell Mol Immunol 8, 157–163 (2011). https://doi.org/10.1038/cmi.2010.35

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