[HTML][HTML] Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

KH Chen, M Wada, AE Firor, KG Pinz, A Jares, H Liu… - Oncotarget, 2016 - ncbi.nlm.nih.gov
KH Chen, M Wada, AE Firor, KG Pinz, A Jares, H Liu, H Salman, M Golightly, F Lan, X Jiang…
Oncotarget, 2016ncbi.nlm.nih.gov
Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very
aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient
outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the
standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has
shown in B-cell malignancies to be an effective curative option and this extends promise into
treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is …
Abstract
Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design. We engineered a robust 3 rd generation anti-CD3 CAR construct (CD3CAR) into an NK cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival. In this study, we present the CAR directed targeting of a novel target-CD3 using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and potential for new therapeutic approaches that could improve the current standard of care for PTCLs.
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