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

34 Citations (Scopus)

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

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Neoplasm Antigens
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunotherapy
Pediatrics
T-Lymphocytes
Cell Line
National Cancer Institute (U.S.)
Antigens
Recurrence
Peptide Library
Hematopoietic Stem Cell Transplantation
Autoantigens
Lymphocyte Count
Coculture Techniques
Dendritic Cells
Blood Cells
Leukemia
Research Design
Drug Therapy
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia-implications for immunotherapy. / Weber, Gerrit; Caruana, Ignazio; Rouce, Rayne H.; Barrett, A. John; Gerdemann, Ulrike; Leen, Ann M.; Rabin, Karen R.; Bollard, Catherine M.

In: Clinical Cancer Research, Vol. 19, No. 18, 15.09.2013, p. 5079-5091.

Research output: Contribution to journalArticle

Weber, Gerrit ; Caruana, Ignazio ; Rouce, Rayne H. ; Barrett, A. John ; Gerdemann, Ulrike ; Leen, Ann M. ; Rabin, Karen R. ; Bollard, Catherine M. / Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia-implications for immunotherapy. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 18. pp. 5079-5091.
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