Article citationsMore>>
R. J. Brentjens, I. Riviere, J. H. Park, M. L. Davila, X. Wang, J. Stefanski, C. Taylor, R. Yeh, S. Bartido, O. Borquez-Ojeda, M. Olszewska, Y. Bernal, H. Pegram, M. Przybylowski, D. Hollyman, Y. Usachenko, D. Pirraglia, J. Hosey, E. Santos, E. Halton, P. Maslak, D. Scheinberg, J. Jurcic, M. Heaney, G. Heller, M. Frattini and M. Sadelain, “Safety and Persistence of Adoptively Transferred Autologous CD19-Targeted T Cells in Patients with Relapsed or Chemotherapy Refractory B-Cell Leukemias,” Blood, Vol. 118,
has been cited by the following article:
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TITLE:
Rejection of Experimental Hodgkins Lymphoma by T-Cells Engineered with a CD19 Chimeric Antigen Receptor
AUTHORS:
Anna Swanson, Eleanor Cheadle, David Gilham, Dorothy Crawford, Simon Talbot, Ingo Johannessen
KEYWORDS:
Hodgkin’s Lymphoma; CD19; Chimeric Antigen Receptor; Immunotherapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.3 No.5,
October
18,
2012
ABSTRACT: T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.
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