title: Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.
abstract: Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources.
authors: Division of Cancer Medicine, M.D. Anderson Cancer Center, Houston, TX 77005, USA.
authors: Partow
authors: P
authors: Kebriaei
authors: Helen
authors: H
authors: Huls
authors: Bipulendu
authors: B
authors: Jena
authors: Mark
authors: M
authors: Munsell
authors: Rineka
authors: R
authors: Jackson
authors: Dean A
authors: DA
authors: Lee
authors: Perry B
authors: PB
authors: Hackett
authors: Gabriela
authors: G
authors: Rondon
authors: Elizabeth
authors: E
authors: Shpall
authors: Richard E
authors: RE
authors: Champlin
authors: Laurence J N
authors: LJ
authors: Cooper
mesh_terms: D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002478:Cells, Cultured; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
chemical_list: D018941:Antigens, CD19; D018106:CD28 Antigens; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins