Generating peripheral blood derived lymphocytes reacting against autologous primary AML blasts

Rohtesh S. Mehta, Xiaohua Chen, Jeyaraj Antony, Michael Boyiadzis, Paul Szabolcs

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)- reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-γ-treated autologous AML weekly×3, interleukin-15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid-derived suppressor cells. We discuss our approach to creating primary AML-reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalJournal of Immunotherapy
Volume39
Issue number2
DOIs
StatePublished - 2016

Keywords

  • AML
  • Acute leukemia
  • Adoptive immunotherapy
  • Autologous CTLs
  • Cellular therapy
  • Cytotoxic
  • MDSC
  • T
  • T cells

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