title: Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts.
abstract: Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)-reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-γ-treated autologous AML weekly × 3, interleukin-15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid-derived suppressor cells. We discuss our approach to creating primary AML-reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells.
authors: *Division of Blood and Marrow Transplantation and Cellular Therapies, Children's Hospital of Pittsburgh of UPMC †University of Pittsburgh Cancer Institute ‡Department of Immunology, University of Pittsburgh, Pittsburgh, PA.
authors: Rohtesh S
authors: RS
authors: Mehta
authors: Xiaohua
authors: X
authors: Chen
authors: Jeyaraj
authors: J
authors: Antony
authors: Michael
authors: M
authors: Boyiadzis
authors: Paul
authors: P
authors: Szabolcs
mesh_terms: D001324:Autoantigens / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D006801:Humans; D056747:Immunomodulation; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D022423:Myeloid Cells / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059467:Transcriptome
chemical_list: D001324:Autoantigens; D007371:Interferon-gamma