ZCH-2B8a, an antibody targeting actin-binding protein coronin-1a, is a potential therapeutic agent for B-lineage malignancies

Abstract

Background: Monoclonal antibody (mAb)-based targeted therapy is one of the most promising strategies to cure cancers. MAb ZCH-2B8a (2B8a) was a novel antibody generated in our laboratory, which presented potential to be a therapeutic agent for hematologic malignancies.

Methods: We investigated the reactivity profile of 2B8a mAb, identified the targeting antigen by proteomic and genetic approaches and evaluated its potential to exert tumor cell killing.

Results: 2B8a antigen was strictly expressed on lymph tissues and hematopoietic cells (mainly leukocytes), and was highly expressed on B-lineage leukemia cell lines and acute lymphoblastic leukemia (ALL) cells from patients. 2B8a antibody was quickly internalized into the target cells once binding to the antigen, but was capable of killing tumor cells through complement dependent cytotoxicity. To identify the 2B8a antigen, the proteins of Raji cells were immunoprecipitated with 2B8a antibody and analyzed by mass spectrometry, which indicated that coronin-1a was a potential candidate. Then, coronin-1a gene was cloned from Raji cells, inserted into plasmid pcDNA3.1 (+), and transfected into CHO cells. The intracellular 2B8a antigen level was significantly increased in the coronin-1a transfectant cell line.

Conclusion: 2B8a mAb is a novel antibody targeting coronin-1a, which has the potential to be a therapeutic agent for B-lineage malignancies.

• Coronin-1a
• internalization
• leukemia
• monoclonal antibody
• targeting therapy