BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors

Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso TrentiFranco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)582-586
Number of pages5
JournalBlood
Volume129
Issue number5
DOIs
Publication statusPublished - Feb 2 2017

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Comoli, P., Basso, S., Riva, G., Barozzi, P., Guido, I., Gurrado, A., Quartuccio, G., Rubert, L., Lagreca, I., Vallerini, D., Forghieri, F., Morselli, M., Bresciani, P., Cuoghi, A., Paolini, A., Colaci, E., Marasca, R., Cuneo, A., Iughetti, L., ... Potenza, L. (2017). BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors. Blood, 129(5), 582-586. https://doi.org/10.1182/blood-2016-07-731091