| Status | 已發表Published |
| 中国免疫学会第九届全国免疫学学术大会 | |
Zhao, Q. ; Ahmed, M.; Tassev, D.V.; Hasan, A.; O'Reilly, R.J.; Cheung, N.V.
| |
| 2014-10-01 | |
| Source Publication | Chimeric antigen receptor therapy of human TCR-like antibodies to intracellular WT 1 oncoprotein
 |
| Pages | 205-206 |
| Publisher | 中国免疫学会第九届全国免疫学学术大会论文集 |
| Abstract | Background:WT1_(126)(RMFPNAPYL)is a human leukocyte antigen-A2(HLA-A2)restricted peptide derived from Wilms tumor protein(WT1),which is widely expressed in a broad spectrum of leukemias,lymphomas and solid tumors.Purpose:A novel T-cell-receptor(TCR)-like fully-human antibody specific for the T cell epitope consisting of the WT1_(126)/HLA-A2 complex was isolated from a human antibody library.This antibody selectively bound and killed WT1(+)and HLA-A2(+)leukemia and solid tumor cell lines.Methods:The TCR-like antibody was affinity-matured by mutagenesis combined with yeast display,and structurallyanalyzed using a homology model.Affinity-maturated antibodies as native proteins or chimeric antigen receptor(CAR)were evaluated in vitro ADCC assays,and leukemia therapeutic models.Results:This monovalent scFv showed a 100-fold affinity improvement(KD=3nM).Bivalent scFv-huIgGl-Fc fusion protein demonstrated an even higher avidity(K_D=2pM)binding to the T cell epitope and was capable of mediating ADCC or tumor lysis by CAR-expressing human T or NK cells.This antibody demonstrated potent cytotoxicity in vivo towards WT1(+)and HLA-A2(+)leukemia xenograft.Conclusions:In summary,we provide a strategy for developing high affinity human TCR-like antibodies targeting intracellular oncogenic proteins for potential clinical therapy. |
| Keyword | WT1 CAR TCR-like antibodies |
| URL | View the original |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 55680 |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES |
| Corresponding Author | Zhao, Q. |
| Recommended Citation GB/T 7714 | Zhao, Q.,Ahmed, M.,Tassev, D.V.,等. 中国免疫学会第九届全国免疫学学术大会[C]:中国免疫学会第九届全国免疫学学术大会论文集, 2014, 205-206. |
| APA | Zhao, Q.., Ahmed, M.., Tassev, D.V.., Hasan, A.., O'Reilly, R.J.., & Cheung, N.V. (2014). 中国免疫学会第九届全国免疫学学术大会. Chimeric antigen receptor therapy of human TCR-like antibodies to intracellular WT 1 oncoprotein, 205-206. |
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