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A preparation of autologous CD4+ and CD8+ T-lymphocytes gene-edited to integrate a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 and to eliminate the programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1) gene, with potential immunomodulating and antineoplastic activities. Upon administration, autologous PD1-knockout CD19-specific CAR T cells specifically target and bind to CD19-expressing tumor cells, thereby selectively lysing CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies. Expression of PD-1, an inhibitory receptor expressed on activated T-cells, plays a key role in CTL suppression, T-cell exhaustion and CTL apoptosis. PD-1 knockout may abrogate T-cell exhaustion and increase T-cell activity and cytotoxicity.
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