Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia.
Twenty-two patients with acute myeloid leukaemia were recruited into a phase I/II clinical trial investigating the vaccination of patients in complete remission (CR) with autologous dendritic-like leukaemia cells (DLLC). At trial entry, leukaemia cells were harvested and tested for their ability to undergo cytokine-induced dendritic cell differentiation. Patients were then treated with intensive chemotherapy. Five patients achieved both CR and had leukaemia cells that successfully underwent differentiation and therefore proceeded to vaccination. Four escalating doses of DLLC were administered weekly by subcutaneous injection. Vaccination was generally well tolerated although one patient developed extensive eczema and an increased antinuclear factor titre possibly indicating induction of autoimmunity. Development of anti-leukaemic T-cell responses was assessed by enzyme-linked immunospot analysis of gamma-interferon secreting T lymphocytes and by human leucocyte antigen tetramer analysis for WT1-specific T cells. Increases in anti-leukaemic T-cell responses were demonstrated in four patients, but only two of the five remained in remission more than 12 months postvaccination. The study has demonstrated that generation of DLLC is feasible in only a subgroup of patients and is currently neither broadly applicable or clinically effective.
Roddie
H
H
Haematology Department, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. huw.roddie@luht.scot.nhs.uk
Klammer
M
M
Thomas
C
C
Thomson
R
R
Atkinson
A
A
Sproul
A
A
Waterfall
M
M
Samuel
K
K
Yin
J
J
Johnson
P
P
Turner
M
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects / Q000379:methods
D019496:Cancer Vaccines; D007371:Interferon-gamma