title: Genetically engineered donor T cells to optimize graft-versus-tumor effects across MHC barriers.
abstract: Hematopoietic stem cell transplantation has been used for more than 50 years to combat hematologic malignancies. In addition to being the first stem cell therapy, transplantation has provided evidence for the potent anti-tumor effects of T cells. Facilitating T-cell-based immunity against malignancies requires a careful balancing act between generating a robust response and avoiding off-target killing of healthy tissues, which is difficult to accomplish using bulk donor T cells. To address these issues, several approaches have been developed, drawing on basic T-cell biology, to potentiate graft-versus-tumor activity while avoiding graft-versus-host disease. Current strategies for anti-tumor cell therapies include: (i) selecting optimal T cells for transfer; (ii) engineering T cells to possess enhanced effector functions; and (iii) generating T-cell precursors that complete development after adoptive transfer. In this review, we assess the current state of the art in T-lineage cell therapy to treat malignancies in the context of allogeneic hematopoietic stem cell transplantation.
authors: Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Arnab
authors: A
authors: Ghosh
authors: Amanda M
authors: AM
authors: Holland
authors: Marcel R M
authors: MR
authors: van den Brink
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003602:Cytotoxicity, Immunologic; D005818:Genetic Engineering; D020350:Graft vs Tumor Effect / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens
keywords: GVHD; GVT; PLZF; TRAIL; allo-HSCT; precursor T cells