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Generation of CD20-specific TCRs for TCR gene therapy of CD20low B-cell malignancies insusceptible to CD20-targeting antibodies.

Oncotarget. 2016; 
JahnLorenz,van der SteenDirk M,HagedoornRenate S,HombrinkPleun,KesterMichel G D,SchoonakkerMarjolein P,de RidderDaniëlle,van VeelenPeter A,FalkenburgJ H Frederik,HeemskerkMirjam
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摘要

Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20. We isolated CD8+ T-cell clones binding to peptide-MHC-tetramers composed of HLA-A*02:01 and CD20-derived peptide SLFLGIL... More

关键词

B-cell leukemia and lymphoma,CD20,TCR gene transfer,immunotherapy,monoclonal antibo