Studies from Memorial Sloan Kettering Cancer Center, Department of Medicine describe new findings in acute lymphoblastic leukemia therapy
2007 NOV 19 -- Data detailed in 'Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts' have been presented. "Human T cells targeted to the B cell-specific CD19 antigen through retroviral-mediated transfer of a chimeric antigen receptor (CAR), termed 19z1, have shown significant but partial in vivo antitumor efficacy in a severe combined immunodeficient (SCID)-Beige systemic human acute lymphoblastic leukemia (NALM-6) tumor model. Here, we investigate the etiologies of treatment failure in this model and design approaches to enhance the efficacy of this adoptive strategy A panel of modified CD19-targeted CARs designed to deliver combined activating and costimulatory signals to the T cell was generated and tested in vitro to identify an optimal second-generation CAR," scientists writing in the journal Clinical Cancer Research report. "Antitumor efficacy of T cells expressing this optimal costimulatory CAR, 19-28z, was analyzed in mice bearing systemic costimulatory ligand-deficient NALM-6 tumors Expression of the 19-28z CAR, containing the signaling domain of the CD28 receptor, enhanced systemic T-cell antitumor activity when compared with 19z1 in treated mice. A treatment schedule of 4 weekly T-cell injections, designed to prolong in vivo T-cell function, further improved long-term survival. Bioluminescent imaging of tumor in treated mice failed to identify a conserved site of tumor relapse, consistent with successful homing by tumor-specific T cells to systemic sites of tumor involvement Both in vivo costimulation and repeated administration enhance eradication of systemic tumor by genetically targeted T cells," wrote R.J. Brentjens and colleagues, Memorial Sloan Kettering Cancer Center, Department of Medicine. The researchers concluded: "The finding that modifications in CAR design as well as T-cell dosing allowed for the complete eradication of systemic disease affects the design of clinical trials using this treatment strategy." Brentjens and colleagues published their study in Clinical Cancer Research (Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clinical Cancer Research, 2007;13(18 Pt 1):5426-35). Additional information can be obtained by contacting R.J. Brentjens, Memorial Sloan Kettering Cancer Center, Dept. of Medicine, New York, New York 10021 USA.. The publisher of the journal Clinical Cancer Research can be contacted at: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA. Keywords: United States, New York, Acute Lymphoblastic Leukemia Therapy, Acute Lymphoblastic Leukemia, Cancer, Cancer Research, Hematology, Oncology, Therapy, Treatment. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
|
