Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response.
Recently, we described that vaccination with allogeneic dendritic cells (DCs) pulsed with tumor cell lysate generated specific CD8+ T cell response in patients with B-cell chronic lymphocytic leukemia (B-CLL). In the present study, the potential of autologous DCs pulsed ex vivo with tumor cell lysates to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Twelve patients at clinical stage 0-2 as per Rai were vaccinated intradermally up to eight times with a mean number of 7.4 x 10(6) DCs pulsed with B-CLL cell lysate. We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination. A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination. In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4+CD25(+)FOXP3+ T regulatory cells were observed. Taken together, the study demonstrated that vaccination with autologous DC in CLL patients is feasible and safe. Immunological and to some extend hematological responses could be noted, justifying further investigation on this immunotherapeutical approach.
Hus
I
I
Department of Hematooncology, Medical University of Lublin, Lublin, Poland.
Schmitt
M
M
Tabarkiewicz
J
J
Radej
S
S
Wojas
K
K
Bojarska-Junak
A
A
Schmitt
A
A
Giannopoulos
K
K
Dmoszyńska
A
A
Roliński
J
J
D000368:Aged; D000951:Antigens, Neoplasm / Q000627:therapeutic use; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000637:transplantation*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018664:Interleukin-12