Combined use of dendritic cells enhances specific antileukemia immunity by leukemia cell-derived heat shock protein 70 in a mouse model with minimal residual leukemia cells.
We have reported that immunotherapy using leukemia cell-derived heat shock proteins (HSPs) is effective against minimal residual disease (MRD) after syngeneic stem cell transplantation (SCT) in mice. However, leukemia patients after SCT are usually immunocompromised and immunologically tolerant to leukemia cells. We investigated whether the use of dendritic cells (DCs) in combination with HSP70 enhances cytotoxicity against B-cell leukemia cell line A20 in mice after syngeneic SCT. All unimmunized mice died of leukemia early after A20 cell inoculation, whereas mice immunized with HSP70 or HSP70-pulsed DCs survived significantly longer. Although only 60% of the HSP70-immunized mice survived, all mice immunized with HSP70-pulsed DCs survived without MRD. In addition, the cytotoxicities against A20 cells for splenocytes from mice immunized with HSP70-pulsed DCs were significantly higher than those of HSP70-immunized mice, and the cytotoxicities against A20 cells were significantly blocked by anti-CD8 antibody and by major histocompatibility complex class I antibody, but not by anti-CD4 antibody. Moreover, abnormalities were detected in neither the biochemical data nor the histopathologic findings. These findings indicate that the combined use of DCs and leukemia cell-derived HSP70 enhances the antileukemia effect by inducing the specific cytotoxicities of CD8+ cytotoxic T-cells, thereby eradicating MRD effectively and safely, even in an immunocompromised state after syngeneic SCT. This approach may thus be useful for further application of HSP in leukemia patients after autologous SCT.
Iuchi
Yasuyuki
Y
Division of Gastroenterology and Hematology/Oncology, Department of Medicine Asahikawa Medical College, Asahikawa, Japan.
Torimoto
Yoshihiro
Y
Sato
Kazuya
K
Tamura
Yasuaki
Y
Jimbo
Junko
J
Inamura
Junki
J
Shindo
Motohiro
M
Ikuta
Katsuya
K
Ohnishi
Kouhei
K
Kohgo
Yutaka
Y
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004195:Disease Models, Animal; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000276:immunology*; D018365:Neoplasm, Residual; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D014185:Transplantation, Isogeneic; D014611:Vaccination
D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins