CTLA-4 blockade by a human MAb enhances the capacity of AML-derived DC to induce T-cell responses against AML cells in an autologous culture system

Cytotherapy. 2006;8(1):3-12. doi: 10.1080/14653240500499507.


Background: Cells from AML patients can differentiate into the phenotype of DC when cultured with GM-CSF and IL-4. Such cytokine-treated AML-derived DC (AML-DC) can stimulate autologous T cells. In this study we examined whether an anti-CTLA-4 MAb (MDX-010) could enhance the generation of autologous anti-AML T cells.

Methods: MAb MDX-010 was added to AML PBMC cultures in the presence of GM-CSF and IL-4, a previously reported AML-DC culture method of generating anti-AML T cells. T-cell activation and proliferation were examined thereafter.

Results: Addition of MDX-010 to GM-CSF/IL-4-conditioned AML-DC cultures induced a mean seven-fold increase in the numbers of autologous T cells compared with cultures without MDX-010 (P < 0.007). T cells stimulated by AML-DC with CTLA-4 blockade were significantly more cytotoxic towards autologous AML cells than those without MDX-010 (42 +/- 23% vs. 26 +/- 15%, E:T ratio of 20). T cells stimulated by AML-DC with CTLA-4 blockade had significantly greater proportions of T cells producing IFN-gamma in response to autologous AML cells than those cultured with AML-DC alone (10.7 +/- 4.7% vs. 4.5 +/- 2.4% for CD4+ IFN-gamma+ CD69+ and 9.8 +/- 4.1% vs. 4 +/- 2.1% for CD8+ IFN-gamma+ CD69+ with or without MDX-010; n = 7; P < 0.007, P < 0.003, respectively).

Discussion: CTLA-4 blockade enhances the activity and numbers of AML-reactive T cells that can be stimulated by autologous AML-DC and may enhance the efficacy of adoptive immunotherapy of AML.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD
  • Antigens, Differentiation / immunology*
  • Antigens, Differentiation / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen
  • Cell Culture Techniques
  • Cell Proliferation
  • Culture Media, Conditioned
  • Cytotoxicity, Immunologic / drug effects
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • Humans
  • Interferon-gamma / metabolism
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / pathology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Receptors, Interleukin-2 / metabolism
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Culture Media, Conditioned
  • Receptors, Interleukin-2
  • Interferon-gamma