| Autor: |
Ying Shen, Yi-Ming Li, Jing-Jing Zhou, Zhan Zhou, Ying-Chun Xu, Wen-Bin Zhao, Shu-Qing Chen |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences, Vol 20, Iss 16, p 3912 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1422-0067 |
| DOI: |
10.3390/ijms20163912 |
| Popis: |
Wilms tumor 1 (WT1) oncoprotein is an intracellular oncogenic transcription factor which is barely expressed in normal adult tissues but over expressed in a variety of leukemias and solid cancers. WT1-derived HLA-A*02:01 T cell epitope, RMFPNAPYL (RMF), is a validated target for T cell-based immunotherapy. We generated two T cell receptor mimic antibody-drug conjugates (TCRm-ADCs), ESK-MMAE, and Q2L-MMAE, against WT1 RMF/HLA-A*02:01 complex with distinct affinities, which mediate specific antitumor activity. Although ESK-MMAE showed higher tumor growth inhibition ratio in vivo, the efficacy of them was not so promising, which might be due to low expression of peptide/HLA targets. Therefore, we explored a bispecific TCRm-ADC that exerted more potent tumor cytotoxicity compared with TCRm-ADCs. Hence, our findings validate the feasibility of the presenting intracellular peptides as the targets of ADCs, which broadens the antigen selection range of antibody-based drugs and provides new strategies for precision medicine in tumor therapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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