BACKGROUND: No effective therapeutic modalities exist for the treatment of relapsed high risk acute lymphoblastic leukemia (ALL). Adoptive cellular immunotherapy by transfusion of polyclonal donor lymphocytes is not always effective and is limited by cellular cross-reactivity with normal tissues, leading to development of clinical graft-versus-host disease (GVHD). METHOD: To develop an immunotherapeutic strategy for targeted elimination of residual leukemic blasts, human T cells were gene-modified to express CD19-specific chimeric receptors. RESULTS: Gene-modified T cells specifically lyse CD19-expressing lymphatic blast cells, however, they show a limited proliferative response to stimulation with CD19. Integration of the signal transduction domain of the costimulatory molecule CD28 enhances the proliferative properties of the gene-modified T cells. CONCLUSIONS: Adoptive transfer of gene-modified virus-specific T cells may provide a useful strategy for prevention and early treatment of ALL relapses following allogeneic stem cell transplantation.
BACKGROUND: No effective therapeutic modalities exist for the treatment of relapsed high risk acute lymphoblastic leukemia (ALL). Adoptive cellular immunotherapy by transfusion of polyclonal donor lymphocytes is not always effective and is limited by cellular cross-reactivity with normal tissues, leading to development of clinical graft-versus-host disease (GVHD). METHOD: To develop an immunotherapeutic strategy for targeted elimination of residual leukemic blasts, human T cells were gene-modified to express CD19-specific chimeric receptors. RESULTS: Gene-modified T cells specifically lyse CD19-expressing lymphatic blast cells, however, they show a limited proliferative response to stimulation with CD19. Integration of the signal transduction domain of the costimulatory molecule CD28 enhances the proliferative properties of the gene-modified T cells. CONCLUSIONS: Adoptive transfer of gene-modified virus-specific T cells may provide a useful strategy for prevention and early treatment of ALL relapses following allogeneic stem cell transplantation.
Authors: S Gattenlöhner; H Jörissen; M Huhn; A Vincent; D Beeson; S Tzartos; A Mamalaki; B Etschmann; H K Muller-Hermelink; E Koscielniak; S Barth; A Marx Journal: J Biomed Biotechnol Date: 2010-02-24
Authors: David C Bishop; Ning Xu; Benjamin Tse; Tracey A O'Brien; David J Gottlieb; Alla Dolnikov; Kenneth P Micklethwaite Journal: Mol Ther Date: 2018-06-01 Impact factor: 11.454
Authors: Kenneth P Micklethwaite; Barbara Savoldo; Patrick J Hanley; Ann M Leen; Gail J Demmler-Harrison; Laurence J N Cooper; Hao Liu; Adrian P Gee; Elizabeth J Shpall; Cliona M Rooney; Helen E Heslop; Malcolm K Brenner; Catherine M Bollard; Gianpietro Dotti Journal: Blood Date: 2010-01-28 Impact factor: 22.113
Authors: David L Porter; Edwin P Alyea; Joseph H Antin; Marcos DeLima; Eli Estey; J H Frederik Falkenburg; Nancy Hardy; Nicolaus Kroeger; Jose Leis; John Levine; David G Maloney; Karl Peggs; Jacob M Rowe; Alan S Wayne; Sergio Giralt; Michael R Bishop; Koen van Besien Journal: Biol Blood Marrow Transplant Date: 2010-08-10 Impact factor: 5.742
Authors: A Bister; T Ibach; C Haist; G Gerhorst; D Smorra; M Soldierer; K Roellecke; M Wagenmann; K Scheckenbach; N Gattermann; C Wiek; H Hanenberg Journal: Mol Ther Oncolytics Date: 2022-06-06 Impact factor: 6.311
Authors: Yuan Ji; Lei Feng; Ping Liu; Elizabeth J Shpall; Partow Kebriaei; Richard Champlin; Donald Berry; Laurence J N Cooper Journal: J Biopharm Stat Date: 2012 Impact factor: 1.051