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N. M. Haynes, J. A. Trapani, M. W. Teng, J. T. Jackson, L. Cerruti, S. M. Jane, M. H. Kershaw, M. J. Smyth and P. K. Darcy, “Single-Chain Antigen Recognition Receptors That Costimulate Potent Rejection of Established Experimental Tumors,” Blood, Vol. 100, No. 10, 2002, pp. 3155-3163. doi:10.1182/blood-2002-04-10411

has been cited by the following article:

• 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.