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Clin Cancer Res. 2013 Sep 15;19(18):5079-91. doi: 10.1158/1078-0432.CCR-13-0955. Epub 2013 Jul 9.

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

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1
Authors' Affiliations: Center for Cell and Gene Therapy, Departments of Pediatrics, Medicine, and Immunology, Baylor College of Medicine; The Methodist Hospital; Texas Children's Hospital; Texas Children's Cancer Center, Houston, Texas; and Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.

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 (51)Cr-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.

PMID:
23838315
PMCID:
PMC3778051
DOI:
10.1158/1078-0432.CCR-13-0955
[Indexed for MEDLINE]
Free PMC Article
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