A Novel Monoclonal Antibody to PL2L60 is Effective For Therapy of Various Types of Cancers in Human and Mice

Abstract Background: PL2L60 is a PIWIL2-like (PL2L) protein that is specifically and widely expressed in various types of hematopoietic and solid tumors. However, it is unknown whether PL2L60 is an effective target for cancer immunotherapy. The current study aimed to investigate the efficacy of an monoclonal antibody (mAb) to PL2L60 (clone KAO3；IgM isotype) in treatment of the cancers either from human or mouse.Methods: The expression of PL2L60 protein in the cell surface and cytoplasm were determined in a panel of human and mouse tumor cell lines by flow cytometry, immunofluorescent staining and Western Blotting. The apoptosis and the cell cycle arrest of the tumor cells treated with mAb KAO3 were evaluated by flow cytometry. The tumorigenesis of the mAb KAO3-pretreated tumor cells was determined by tumor incidence and tumor size, and efficacy of mAb KAO3 treatment on tumor growth in tumors-bearing mice were kinetically evaluated. Complement-dependent cytotoxicity tests were utilized to determine the mechanism of mAb KAO3 killing tumor cells. Results: Treatment of human or mouse tumor cells with mAb KAO3 at the time of inoculation efficiently inhibited their tumorigenesis in the immunodeficient mice. Moreover, injection of mAb KAO3 into established tumors significantly inhibited their growth, and prolonged survival of the tumor-bearing mice, including lymphoma, breast cancer, lung cancer and cervical cancer. The inhibitory effects of mAb KAO3 were likely associated with its binding to the PL2L60 expressed on tumor cell surface, which may induce cell apoptosis through either activation of complement or blocking cell cycling. The cell cycling was arrested at G2/M phase and DNA synthesis may be inhibited.Conclusion: We have identified the PL2L60 as a novel tumor-specific and broad-spectral biomarker, which is recognized by the mAb KAO3 as an efficient target for immunotherapy of both solid and hematopoietic cancers.