Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts.
Vaccination with dendritic cells (DCs) as professional antigen presenting cells generated from autologous leukemic blasts might elicit anti-leukemic T cell responses in patients with acute myeloid leukemia (AML). To test this hypothesis, autologous AML-DC were generated under good manufacturing practice (GMP) conditions and injected s.c. into five AML patients up to four times at a biweekly interval. No severe adverse side effects were observed. Three patients remained in a stable condition for 5.5-13 months and two patients died from rapidly progressive AML. Compared to the initial T cell frequency, enzyme linked immunosorbent spot (ELISPOT) assays revealed a significant increase of granzyme B releasing CD8+ T cells specifically recognizing the PRAME derived peptide (ALYVDSLFFL), a leukemia associated antigen expressed by AML blasts. The cytokine levels in the serum of vaccination AML patients as assessed by cytokine bead assay changed over the period of vaccination to an elevated type 1 T helper cell pattern. Interferon gamma production by CD4+ T helper cells increased during vaccination. In summary, we demonstrated that autologous AML-DC vaccination is well tolerated and can result in an enhanced and specific response of cytotoxic T cells in AML patients.
Li
Li
L
Department of Internal Medicine III, University of Ulm, D-89081 Ulm, Germany.
Giannopoulos
Krzysztof
K
Reinhardt
Peter
P
Tabarkiewicz
Jacek
J
Schmitt
Anita
A
Greiner
Jochen
J
Rolinski
Jacek
J
Hus
Iwona
I
Dmoszynska
Anna
A
Wiesneth
Markus
M
Schmitt
Michael
M
D000208:Acute Disease; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000032:analysis; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014611:Vaccination / Q000379:methods; D000097802:CD83 Antigen
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051940:B7-2 Antigen; D053804:Granzymes; D007136:Immunoglobulins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016753:Interleukin-10; D007376:Interleukin-2; D015847:Interleukin-4; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D012697:Serine Endopeptidases; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C404944:PRAME protein, human; C509213:GZMB protein, human