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Methods of dendritic cell preparation for acute lymphoblastic leukemia immunotherapy in children

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Abstract

Cell immunotherapy through dendritic cells (DC) presents a hopeful strategy for the treatment of various tumors. The aim of our study was to find which progenitor cells are most suitable for the preparation of dendritic cells in acute lymphoblastic leukemia (ALL) in pediatric patients, whether blasts from bone marrow or dendritic cells generated from peripheral blood mononuclear cells taken at the time of remission after induction chemotherapy. DC generated from the BM blasts of patients with B-ALL and T-ALL (n=15) at the time of diagnosis expressed low levels of costimulatory molecules and CD markers typical for mature DC. In contrast, DC cultivated from peripheral mononuclear cells of patients (n=9) had comparable morphology and expression of costimulatory molecules to DC obtained from healthy individuals, which was even higher after tumor lysate pulsing. Autologous lymphocyte proliferation increased after DC blasts lysate pulsation and further after lymphocyte restimulation, showing evidence of induction of specific cytotoxic lymphocytes. When comparing both cell sources for the preparation of DC in patients with ALL, it appears that peripheral mononuclear cells obtained after chemotherapy are more suitable than bone marrow leukemic blasts due to similar morphology, phenotypic, and functional capacity to monocytes of healthy donors. Despite this, it is necessary to take into account individual variability when preparing DC-based vaccines. The final verification of the efficiency of immunotherapy against residual hematopoietic malignant cells in patients with ALL can only be obtained through a clinical study.

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References

  1. Pui CH. Childhood leukemias. N Engl J Med 1995; 332:1618–1630.

    Article  PubMed  CAS  Google Scholar 

  2. Campana D, Neale GA, Coustan-Smith E, Pui CH. Detection of minimal residual disease in acute lymphoblastic leukemia: the St Jude experience. Leukemia 2001; 15:278–279.

    Article  PubMed  CAS  Google Scholar 

  3. Potter MN, Steward CG, Oakhill A. The significance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia. Br J Haematol 1993; 83:412–418.

    PubMed  CAS  Google Scholar 

  4. Costello RT, Rey J, Fauriat C, Gastaut JA, Olive D. New approaches in the immunotherapy of haematological malignancies. Eur J Haematol 2003; 70:333–345.

    Article  PubMed  CAS  Google Scholar 

  5. Kedar E, Klein E. Cancer immunotherapy: are the results discouraging? Can they be improved? Adv Cancer Res 1992; 59:245–322.

    Article  PubMed  CAS  Google Scholar 

  6. Champlin R. Separation of graft-vs.-host disease and graft-vs.-leukemia effect against chronic myelogenous leukemia. Exp Hematol 1995; 23:1148–1151.

    PubMed  CAS  Google Scholar 

  7. Celluzzi CM, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD, Jr. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity [see comments]. J Exp Med 1996; 183:283–287.

    Article  PubMed  CAS  Google Scholar 

  8. Tsai V, Kawashima I, Keogh E, Daly K, Sette A, Celis E. In vitro immunization and expansion of antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy using peptide-pulsed dendritic cells. Crit Rev Immunol 1998; 18:65–75.

    PubMed  CAS  Google Scholar 

  9. Murphy GP, et al. Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment. Prostate 1999; 39:54–59.

    Article  PubMed  CAS  Google Scholar 

  10. Holtl L, et al. Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. J Urol 1999; 161:777–782.

    Article  PubMed  CAS  Google Scholar 

  11. Nestle FO, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells [see comments]. Nat Med 1998; 4:328–332.

    Article  PubMed  CAS  Google Scholar 

  12. Panelli MC, et al. Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother 2000; 23:487–498.

    Article  PubMed  CAS  Google Scholar 

  13. Choudhury A, et al. Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 1997; 89:1133–1142.

    PubMed  CAS  Google Scholar 

  14. Choudhury BA, et al. Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood 1999; 93:780–786.

    PubMed  CAS  Google Scholar 

  15. Vuillier F, Maloum K, Thomas EK, Jouanne C, Dighiero G, Scott-Algara D. Functional monocyte-derived dendritic cells can be generated in chronic lymphocytic leukaemia. Br J Haematol 2001; 115:831–844.

    Article  PubMed  CAS  Google Scholar 

  16. Spisek R, et al. Induction of leukemia-specific cytotoxic response by cross-presentation of late-apoptotic leukemic blasts by autologous dendritic cells of nonleukemic origin. Cancer Res 2002; 62:2861–2868.

    PubMed  CAS  Google Scholar 

  17. Harrison BD, Adams JA, Briggs M, Brereton ML, Yin JA. Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia. Blood 2001; 97:2764–2771.

    Article  PubMed  CAS  Google Scholar 

  18. Cardoso AA, et al. Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies. Blood 1999; 94:3531–3540.

    PubMed  CAS  Google Scholar 

  19. Cignetti A, Bryant E, Allione B, Vitale A, Foa R, Cheever MA. CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood 1999; 94:2048–2055.

    PubMed  CAS  Google Scholar 

  20. Osman Y, et al. Activation of autologous or HLA-identical sibling cytotoxic T lymphocytes by blood derived dendritic cells pulsed with tumor cell extracts. Oncol Rep 1999; 6:1057–1063.

    PubMed  CAS  Google Scholar 

  21. Mohty M, et al. Generation of potent T(h)1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells. Int Immunol 2002; 14:741–750.

    Article  PubMed  CAS  Google Scholar 

  22. Pospisilova D, et al. Generation of functional dendritic cells for potential use in the treatment of acute lymphoblastic leukemia. Cancer Immunol Immunother 2002; 51:72–78.

    Article  PubMed  CAS  Google Scholar 

  23. Spisek R, Bretaudeau L, Barbieux I, Meflah K, Gregoire M. Standardized generation of fully mature p70 IL-12 secreting monocyte-derived dendritic cells for clinical use. Cancer Immunol Immunother 2001; 50:417–427.

    Article  PubMed  CAS  Google Scholar 

  24. Panoskaltsis N, Belanger TJ, Liesveld JL, Abboud CN. Optimal cytokine stimulation for the enhanced generation of leukemic dendritic cells in short-term culture. Leuk Res 2002; 26:191–201.

    Article  PubMed  CAS  Google Scholar 

  25. Letarte M, et al. Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med 1988; 168:1247–1253.

    Article  PubMed  CAS  Google Scholar 

  26. Hsu FJ, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2:52–58.

    Article  PubMed  CAS  Google Scholar 

  27. Barratt-Boyes SM, et al. Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol 2000; 164:2487–2495.

    PubMed  CAS  Google Scholar 

  28. Morse MA, Mosca PJ, Clay TM, Lyerly HK. Dendritic cell maturation in active immunotherapy strategies. Expert Opin Biol Ther 2002; 2:35–43.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Immunology, Charles University 2nd Medical Faculty and Faculty Hospital Motol, Prague

    Dagmar Pospíšilová, Jiřina Borovičková, Daniela Rožková, Daniela Seifertová, Zuzana Tobiásová, Radek Špišek & Jirina Bartůnková

  2. Clinic of Paediatric Haematology and Oncology, Charles University 2nd Medical Faculty and Faculty Hospital Motol, Prague

    Jan Stary

Authors
  1. Dagmar Pospíšilová
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  2. Jiřina Borovičková
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  3. Daniela Rožková
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  4. Jan Stary
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  5. Daniela Seifertová
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  6. Zuzana Tobiásová
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  7. Radek Špišek
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  8. Jirina Bartůnková
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Correspondence to Jirina Bartůnková.

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Pospíšilová, D., Borovičková, J., Rožková, D. et al. Methods of dendritic cell preparation for acute lymphoblastic leukemia immunotherapy in children. Med Oncol 22, 79–88 (2005). https://doi.org/10.1385/MO:22:1:079

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  • DOI: https://doi.org/10.1385/MO:22:1:079

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