Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: Preclinical studies

Angelo A. Cardoso, J. Pedro Veiga, Paolo Ghia, Hernani M. Afonso, W. Nicholas Haining, Stephen E. Sallan, Lee M. Nadler

Research output: Contribution to journalArticle

Abstract

We have previously shown that leukemia-specific cytotoxic T cells (CTL) can be generated from the bone marrow of most patients with B-cell precursor acute leukemias. If these antileukemia CTL are to be used for adoptive immunotherapy, they must have the capability to circulate, migrate through endothelium, home to the bone marrow, and, most importantly, lyse the leukemic cells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8+ and exhibit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited and transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells. Additionally, these antileukemia T-cell lines are capable of adhering to autologous stromal cell layers. Finally, autologous antileukemia CTL specifically lyse leukemic cells even in the presence of autologous marrow stroma. Importantly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti-leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and function in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL.

Original languageEnglish
Pages (from-to)3531-3540
Number of pages10
JournalBlood
Volume94
Issue number10
Publication statusPublished - Nov 15 1999

    Fingerprint

ASJC Scopus subject areas

  • Hematology

Cite this

Cardoso, A. A., Veiga, J. P., Ghia, P., Afonso, H. M., Haining, W. N., Sallan, S. E., & Nadler, L. M. (1999). Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: Preclinical studies. Blood, 94(10), 3531-3540.