AUTHOR=Fu Mingpeng , He Qi , Guo Zilong , Zhou Xiaoran , Li Heli , Zhao Liang , Tang Hongling , Zhou Xiaoqi , Zhu Huifen , Shen Guanxin , He Yong , Lei Ping TITLE=Therapeutic Bispecific T-Cell Engager Antibody Targeting the Transferrin Receptor JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01396 DOI=10.3389/fimmu.2019.01396 ISSN=1664-3224 ABSTRACT=

Bispecific T-cell engager antibodies (BiTE) have been explored as a means to recruit cytolytic T cells to kill tumor cells. The transferrin receptor (TfR) is highly expressed on the surface of rapidly proliferating tumor cells. Therefore, it holds great potential in T cell redirecting therapies. In this research, we developed a BiTE targeting TfR and CD3 (TfR-BiTE) and studied its therapeutic impact on TfR-positive cancer. TfR-BiTE had the ability to induce the selective lysis of various TfR-positive cancer cells through the activation of T cells, the release of cytokines, and then the coming proliferation of T cells, whereas TfR-negative cells were not affected. In a subcutaneous HepG2 xenograft model, low concentrations of TfR-BiTE inhibited tumor growth. Overall, these results reveal that TfR-BiTE can selectively deplete TfR-positive HepG2 cells; hence, it represents a novel immunotherapeutic approach for the treatment of hepatocellular carcinoma.