Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.01396
Keywords
bispecific antibodies; T-cell engager; transferrin receptor; tumor immunotherapy; solid tumor
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Funding
- National Natural Science Foundation of China [31570937, 81871391]
- Natural Science Foundation of Hubei Province of China [2017CFB707]
- fundamental research funds for the central universities of China [HUST: 2018KFYYXJJ086]
- Graduates' Innovation Foundation of Huazhong University of Science and Technology [5003510001]
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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.
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