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

2006 ◽  
Vol 84 (5) ◽  
pp. 449-458 ◽  
Author(s):  
Yasuyuki Iuchi ◽  
Yoshihiro Torimoto ◽  
Kazuya Sato ◽  
Yasuaki Tamura ◽  
Junko Jimbo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heat Shock ◽  
Mouse Model ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Combined Use ◽  
Minimal Residual

Combined Use of Dendritic Cells Enhances Specific Anti-Leukemia Effect of Leukemia Cell-Derived-HSP70 in a Mouse Model with Minimal Residual Leukemia Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3065-3065
Author(s):  
Kazuya Sato ◽  
Yoshihiro Torimoto ◽  
Yasuyuki Iuchi ◽  
Yasuaki Tamura ◽  
Junko Jimbo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Bone Marrow Cells ◽  
Leukemia Cell ◽  
Class I ◽  
Biochemical Data ◽  
Leukemia Cells ◽  
Combined Use ◽  
Minimal Residual

Abstract Background: Heat shock proteins (HSPs) are molecular chaperones binding a broad repertorie of endogenous antigenic peptides and carrying them to the MHC. Because the identification of each tumor specific antigen is not necessary, the immunotherapy using HSPs is more practical than other immunological procedures. Meanwhile, relapse due to minimal residual disease (MRD) is a big problem of autologous stem cell transplantation (SCT) against leukemia. We previously reported that immunotherapy using leukemia cell-derived HSPs is effective against MRD after syngeneic bone marrow transplantation (BMT) in mice (Sato et al. Blood, 2001). However, patients receiving SCT are usually immunocompromised due to repeated anti-cancer therapies. Accordingly, it is important to enhance the cytotoxicities (CTXs) against leukemia. Dendritic cells (DCs) are known as professional antigen-presenting cells with a specific receptor for HSPs and are expected to play a major role in immunotherapy. In this study, we evaluated whether the vaccination of DCs pulsed with HSP70 enhances the anti-leukemia effect induced by leukemia cell-derived HSP70 after syngeneic BMT and evaluated the safety of this immunotherapy. Methods: Three class-I-identical mouse tumor cell lines (A20: B-cell leukemia; T27A: myeloid leukemia; colo26: colonic carcinoma) and syngeneic balb/c mice were used in this study. HSP70 was purified from tumor cells. DCs were generated from bone marrow cells cultured with GM-CSF. DCs were pulsed with HSP70 (HSP70-pulsed-DCs) in vitro. Mice were received total body irradiation (TBI) and transplanted bone marrow cells after TBI, then inoculated 2.5 x 104 A20 cells intravenously. HSP70 or HSP70-pulsed-DCs was subcutaneously administrated. Survival days of immunized mice were compared using Kaplan and Meier methods. CTXs of splenocytes against A20 cells were determined by 51Cr release assay. Histological findings of liver and knee joint and biochemical data of serum of immunized mice were investigated. Results: All mice without immunization or immunized with DCs alone died from leukemic dissemination within 90 days after A20 inoculation, whereas mice immunized with A20-derived HSP70 (A20-HSP70) or A20-HSP70-pulsed-DCs survived long significantly. Additionally, although only 60% of the mice immunized with A20-HSP70 survived on day 120, all the mice immunized with A20-HSP70-pulsed-DCs survived with no residual leukemia cells over 120 days. Moreover, splenocytes of mice immunized with A20-HSP70-pulsed-DCs showed significantly higher CTXs against A20 cells in vitro compare to those with A20-HSP70 alone. However, no CTXs against A20 cells were induced by immunization with colo26-or T27A-HSP70-pulsed-DCs. These CTXs against A20 cells were significantly blocked by anti-CD8 and anti-MHC class-I, but not by anti-CD4. Additionally, no abnormal findings were detected either in biochemical data of serum or in histopathology of liver and joint tissue in long term immunized mice. Conclusions: Combined use of dendritic cells with leukemia cell-derived HSP70 enhances anti-leukemia effect by inducing specific cytotoxic activities against leukemia cells, and eradicates MRD effectively and safely even for immunocompromised status after syngeneic BMT. This approach would be useful for a further application of HSP in leukemia-patients after autologous SCT.

scholarly journals Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage

2010 ◽  
Vol 57 (7) ◽  
pp. 844-850 ◽  
Author(s):  
Anatol Manaenko ◽  
Nancy Fathali ◽  
Hank Chen ◽  
Hidenori Suzuki ◽  
Shammah Williams ◽  
...  
Keyword(s):  
Brain Injury ◽  
Heat Shock ◽  
Mouse Model ◽  
Heat Shock Protein ◽  
Intracerebral Hemorrhage ◽  
Heat Shock Protein 70

scholarly journals Resveratrol induces apoptosis in K562 (chronic myelogenous leukemia) cells by targeting a key survival protein, heat shock protein 70

2008 ◽  
Vol 99 (6) ◽  
pp. 1109-1116 ◽  
Author(s):  
Prabir K. Chakraborty ◽  
Soumyajit Banerjee Mustafi ◽  
Sudipto Ganguly ◽  
Mitali Chatterjee ◽  
Sanghamitra Raha
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Chronic Myelogenous Leukemia ◽  
Heat Shock Protein 70 ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Chronic Myelogenous Leukemia Cells

scholarly journals Human recombinant heat shock protein 70 affects the maturation pathways of dendritic cells in vitro and has an in vivo adjuvant activity

2008 ◽  
Vol 84 (1) ◽  
pp. 199-206 ◽  
Author(s):  
Barbara Valentinis ◽  
Annalisa Capobianco ◽  
Francesca Esposito ◽  
Alessandro Bianchi ◽  
Patrizia Rovere-Querini ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Adjuvant Activity
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