title: Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement.
abstract: Treatment of patients with adoptive T-cell therapy requires expansion of unique tumor-infiltrating lymphocyte (TIL) cultures from single-cell suspensions processed from melanoma biopsies. Strategies which increase the expansion and reliability of TIL generation from tumor digests are necessary to improve access to TIL therapy. Previous studies have evaluated artificial antigen presenting cells for their antigen-specific and costimulatory properties. We investigated engineered cells for costimulatory enhancement (ECCE) consisting of K562 cells that express 4-1BBL in the absence of artificial antigen stimulation. ECCE accelerated TIL expansion and significantly improved TIL numbers (P=0.001) from single-cell melanoma suspensions. TIL generated with ECCE contain significantly more CD8CD62L and CD8CD27 T cells then comparable interleukin-2-expanded TIL and maintained antitumor reactivity. Moreover, ECCE improved TIL expansion from nonmelanoma-cell suspensions similar to that seen with melanoma tumors. These data demonstrate that the addition of ECCE to TIL production will enable the treatment of patients that are ineligible using current methods.
authors: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda 20892-1201, MD, USA.
authors: Kevin M
authors: KM
authors: Friedman
authors: Laura E
authors: LE
authors: Devillier
authors: Steven A
authors: SA
authors: Feldman
authors: Steven A
authors: SA
authors: Rosenberg
authors: Mark E
authors: ME
authors: Dudley
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation; D005818:Genetic Engineering; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D020014:K562 Cells / Q000276:immunology; D007694:Killer Cells, Natural / Q000473:pathology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis; D020239:Receptor Cross-Talk / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019076:Transgenes / Q000235:genetics
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D007371:Interferon-gamma