Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematologic and other malignancies
| Autor: | Angela M. Krackhardt, Bernhard Frankenberger, Dirk H. Busch, Ingrid G. Schuster, Elfriede Nössner, Elfriede Eppinger, Elisabeth Kremmer, Christoph Salat, Slavoljub Milosevic, Christian Bogner, Joachim W. Ellwart, Arndt Borkhardt, Christine Hennard, Hans-Jochem Kolb, Christina Kuttler |
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| Rok vydání: | 2007 |
| Předmět: |
Cytotoxicity
Immunologic medicine.medical_treatment Chronic lymphocytic leukemia Immunology Blotting Western Receptors Antigen T-Cell Epitopes T-Lymphocyte Formins Enzyme-Linked Immunosorbent Assay Thymus Gland Biology Biochemistry Peripheral blood mononuclear cell Immunotherapy Adoptive Epitope Antigen Antigens Neoplasm Bone Marrow Cell Line Tumor medicine Humans HLA-A Antigens Reverse Transcriptase Polymerase Chain Reaction T-cell receptor Cell Biology Hematology Immunotherapy medicine.disease Clone Cells Cytoskeletal Proteins Hematologic Neoplasms Leukocytes Mononuclear Stem cell Clone (B-cell biology) Peptides T-Lymphocytes Cytotoxic |
| Zdroj: | Blood. 110(8) |
| ISSN: | 0006-4971 |
| Popis: | Cell-based immunotherapy in settings of allogeneic stem cell transplantation or donor leukocyte infusion has curative potential, especially in hematologic malignancies. However, this approach is severely restricted due to graft-versus-host disease (GvHD). This limitation may be overcome if target antigens are molecularly defined and effector cells are specifically selected. We chose formin-related protein in leukocytes 1 (FMNL1) as a target antigen after intensive investigation of its expression profile at the mRNA and protein levels. Here, we confirm restricted expression in peripheral blood mononuclear cells (PBMCs) from healthy donors but also observe overexpression in different leukemias and aberrant expression in transformed cell lines derived from solid tumors. We isolated allorestricted T-cell clones expressing a single defined TCR recognizing a particular HLA-A2–presented peptide derived from FMNL1. This T-cell clone showed potent antitumor activity against lymphoma and renal cell carcinoma cell lines, Epstein-Barr virus (EBV)–transformed B cells, and primary tumor samples derived from patients with chronic lymphocytic leukemia (CLL), whereas nontransformed cells with the exception of activated B cells were only marginally recognized. Allorestricted TCRs with specificity for naturally presented FMNL1-derived epitopes may represent promising reagents for the development of adoptive therapies in lymphoma and other malignant diseases. |
| Databáze: | OpenAIRE |
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