Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia-implications for immunotherapy

Gerrit Weber, Ignazio Caruana, Rayne H. Rouce, A. John Barrett, Ulrike Gerdemann, Ann M. Leen, Karen R. Rabin, Catherine M. Bollard

Research output: Contribution to journalArticle

Abstract

Purpose: Although modern cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 80%, the outlook remains poor in patients with high-risk disease and those who relapse, especially when allogeneic hematopoietic stem cell transplantation is not feasible. Strategies to improve outcome and prevent relapse are therefore required. Immunotherapy with antigen-specific T cells can have antileukemic activity without the toxicities seen with intensive chemotherapy, and therefore represents an attractive strategy to improve the outcome of high-risk patients with ALL. We explored the feasibility of generating tumor antigen-specific T cells ex vivo from the peripheral blood of 50 patients with ALL [26 National Cancer Institute (NCI) high-risk and 24 standard-risk] receiving maintenance therapy. Experimental Design: Peripheral blood mononuclear cells were stimulated with autologous dendritic cells pulsed with complete peptide libraries of WT1, Survivin, MAGE-A3, and PRAME, antigens frequently expressed on ALL blasts. Results: T-cell lines were successfully expanded from all patients, despite low lymphocyte counts and irrespective of NCI risk group. Antigen-specificity was observed in more than 50% of patients after the initial stimulation and increased to more than 90% after three stimulations as assessed in IFN-γ-enzyme-linked immunospot (ELISpot) and 51Cr-release assays. Moreover, tumor-specific responses were observed by reduction of autologous leukemia blasts in short- and long-term coculture experiments. Conclusion: This study supports the use of immunotherapy with adoptively transferred autologous tumor antigen-specific T cells to prevent relapse and improve the prognosis of patients with high-risk ALL.

Original languageEnglish
Pages (from-to)5079-5091
Number of pages13
JournalClinical Cancer Research
Volume19
Issue number18
DOIs
Publication statusPublished - Sep 15 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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