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EnglishAlthough the emergence of bone marrow (BM)-resident p190BCR-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/priming p190BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with p190BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them 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 allogeneic p190BCR-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 of p190BCR-ABL-specific T cells in the BM. Our results show that p190BCR-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.
| Data di pubblicazione: | 2017 | |
| Titolo: | BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors | |
| Autori: | Comoli, Patrizia; Basso, Sabrina; Riva, Giovanni; Barozzi, Patrizia; Guido, Ilaria; Gurrado, Antonella; Quartuccio, Giuseppe; Rubert, Laura; Lagreca, Ivana; Vallerini, Daniela; Forghieri, Fabio; Morselli, Monica; Bresciani, Paola; Cuoghi, Angela; Paolini, Ambra; Colaci, Elisabetta; Marasca, Roberto; Cuneo, Antonio; Iughetti, Lorenzo; Trenti, Tommaso; Narni, Franco; Foà, Robin; Zecca, Marco; Luppi, Mario; Potenza, Leonardo | |
| Rivista: | BLOOD | |
| Keywords: | Immunology; Biochemistry; Hematology; Cell Biology | |
| Abstract in inglese: | Although the emergence of bone marrow (BM)-resident p190BCR-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/priming p190BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with p190BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them 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 allogeneic p190BCR-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 of p190BCR-ABL-specific T cells in the BM. Our results show that p190BCR-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. | |
| Digital Object Identifier (DOI): | 10.1182/blood-2016-07-731091 | |
| Handle: | http://hdl.handle.net/11392/2370341 | |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
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