A novel tumor-specific broad-spectral monoclonal antibody to PL2L60 is highly effective for the treatment of various types of cancers from human and mouse

Hong-Min Lu; Yu-Jie Fu; Ning Liu; Wu-Yan Xia; Hai-Yan Chen; Meng-Yao Liu; Lin-Feng Li; Jian-Xin Gao

A novel tumor-specific broad-spectral monoclonal antibody to PL2L60 is highly effective for the treatment of various types of cancers from human and mouse

Am J Cancer Res. 2022 Jan 15;12(1):265-279. eCollection 2022.

Authors

Hong-Min Lu^{1

2}, Yu-Jie Fu^{1

3}, Ning Liu¹, Wu-Yan Xia¹, Hai-Yan Chen¹, Meng-Yao Liu¹, Lin-Feng Li¹, Jian-Xin Gao^{1

4}

Affiliations

¹ The State Key Laboratory of Oncogenes and Related Genes, and The Laboratory of Tumorigenesis and Immunity, Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, China.
² Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200127, China.
³ Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200127, China.
⁴ Shanghai Evac Biotechnology Inc. Shanghai 200233, China.

PMID: 35141017
PMCID: PMC8822270

Abstract

There are numerous antibodies used for cancer therapy in clinic, but they are essentially less efficacy than expected. None of them has tumor-specific and broad-spectral properties. PIWIL2-like (PL2L) protein 60 (PL2L60) is a product of alienated activation of PIWIL2 gene, and has been found to be specifically and widely expressed in various types of cancers, including hematopoietic and solid ones. Current study aims to investigate whether a monoclonal antibody (mAb) to PL2L60 has both tumor-specific and broad-spectral properties, which can be used universally to treat various types of cancers. 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 microscopy 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 the efficacy of mAb KAO3 treatment on tumor growth in tumors-bearing mice were kinetically evaluated. Complement-dependent cytotoxicity (CDC) assay was used to determine the capacity of mAb KAO3 to kill tumor cells. Treatment of human or mouse tumor cells from hematopoietic or solid tumors with mAb KAO3 at the time of inoculation efficiently inhibited tumorigenesis in the severe combined immunodeficient (SCID) 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 efficacy of mAb KAO3 treatment is likely associated with its binding to PL2L60 expressed on tumor cell surface, which may lead to cancer cell death through blocking cell cycling and/or activation of complement. In conclusion, we have identified a tumor-specific mAb to PL2L60 (KAO3), which may be used potentially to treat all the types of human cancers including from both hematopoietic and solid ones.

Keywords: PIWIL2; PL2L60; cancer; immunotherapy; mAb KAO3.