title: BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors.
abstract: Although the emergence of bone marrow (BM)-residentp190BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and using them in T-cell therapy strategies. We investigated the feasibility of expanding/primingp190BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed withp190BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease. We report on the feasibility of producing clinical-grade BCR-ABL-specific cytotoxic T lymphocytes (CTLs), endowed with antileukemia activity, from Ph+ALL patients and healthy donors. We treated 3 patients with Ph+ALL with autologous or allogeneicp190BCR-ABL-specific CTLs. No postinfusion toxicity was observed, except for a grade II skin graft-versus-host disease in the patient treated for hematologic relapse. All patients achieved a molecular or hematologic complete remission (CR) after T-cell therapy, upon emergence ofp190BCR-ABL-specific T cells in the BM. Our results show thatp190BCR-ABL-specific CTLs are capable of controlling treatment-refractory Ph+ALL in vivo, and support the development of adoptive immunotherapeutic approaches with BCR-ABL CTLs in Ph+ALL.
authors.affiliation: Pediatric Hematology/Oncology and.|Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.identifier: 0000-0001-5964-0553
authors.initials: P
authors.lastname: Comoli
authors.affiliation: Pediatric Hematology/Oncology and.|Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.
authors.forename: Sabrina
authors.identifier: 0000-0003-2377-815X
authors.initials: S
authors.lastname: Basso
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Riva
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Patrizia
authors.identifier: 0000-0002-8936-1114
authors.initials: P
authors.lastname: Barozzi
authors.affiliation: Pediatric Hematology/Oncology and.|Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guido
authors.affiliation: Pediatric Hematology/Oncology and.|Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Gurrado
authors.affiliation: Pediatric Hematology/Oncology and.|Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Quartuccio
authors.affiliation: Pediatric Hematology/Oncology and.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubert
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Lagreca
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vallerini
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Forghieri
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Morselli
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bresciani
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Cuoghi
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Paolini
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Colaci
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.affiliation: Section of Hematology, University of Ferrara, Ferrara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.affiliation: Section of Pediatric Hemato-Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Iughetti
authors.affiliation: Department of Laboratory Medicine and Pathology, Unità Sociosanitaria Locale, Modena, Italy; and.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Trenti
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Narni
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, Sapienza University, Rome, Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.affiliation: Pediatric Hematology/Oncology and.
authors.forename: Marco
authors.identifier: 0000-0002-8818-1744
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Mario
authors.identifier: 0000-0002-0373-1154
authors.initials: M
authors.lastname: Luppi
authors.affiliation: Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy.
authors.forename: Leonardo
authors.identifier: 0000-0002-2738-6105
authors.initials: L
authors.lastname: Potenza
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation*
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl