Induction of leukemic-cell-specific cytotoxic T lymphocytes by autologous monocyte-derived dendritic cells presenting leukemic cell antigens.

Abstract:

:Leukemic-dendritic cells (leukemic-DCs) have certain limitations, which include difficult generation in 30-40% of patients, and low levels of expression of several key molecules. Therefore, an alternative approach using monocyte-derived DCs pulsed with tumor antigens is required. We investigated the possibility of immunotherapy for AML using leukemic-cell-specific cytotoxic T lymphocytes that were stimulated in vitro by autologous DCs pulsed with tumor antigens. To generate DCs, CD14(+) cells were isolated from peripheral blood mononuclear cells using magnetic-activated cell sorting, and cultured in the presence of GM-CSF and IL-4. On day 6, maturation of DCs was induced by addition of cytokine cocktail (TNF-alpha, IL-1beta, IL-6, and prostaglandin E(2)) for 2 days, and then the mature DCs were pulsed with whole leukemic cell lysates or apoptotic leukemic cells. There were no differences in the phenotypic expressions of mature DCs generated by pulsing with or without leukemic antigens. The mature DCs pulsed with tumor cell lysates or apoptotic leukemic cells showed a higher allostimulatory capacity for allogeneic CD3(+) T cells as compared with mature non-pulsed DCs. Autologous CD3(+) T cells stimulated by the mature pulsed DCs showed more potent cytotoxic activities against autologous leukemic cells than those stimulated by mature non-pulsed DCs. These results suggest that use of DCs pulsed with leukemic cell lysates or apoptotic leukemic cells is a feasible alternative immunotherapeutic approach to overcome the limitations of leukemic-DCs for the treatment of AML patients.

journal_name

J Clin Apher

authors

Lee JJ,Park MS,Park JS,Kang HK,Kim SK,Nguyen Pham TN,Zhu XW,Cho D,Nam JH,Kim YJ,Rhee JH,Chung IJ,Kim HJ

doi

10.1002/jca.20085

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

188-94

issue

3

eissn

0733-2459

issn

1098-1101

journal_volume

21

pub_type

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