| Co-Investigator(Kenkyū-buntansha) |
NAGAI Kojiro Kurume University, Medicine, Assistant, 医学部, 助手 (50299476)
INADA Hiroko Kurume University, Medicine, Assistant, 医学部, 助手 (90223221)
ANDO Akikazu Kurume University, Medicine, Assistant, 医学部, 助手 (80222777)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
As a strategy of the treatment for advanced neuroblastoma, we investigated to clarify a feasibility and potential of the total cell therapy, including not only hematopoietic stem cells, but also immune competent cells, that consists of intensification of initial chemotherapy by earlier induction of stem cell transplantation, CD34 positive selected transplant for elimination of contaminated tumor cells, combination therapy with delayed primary operation and intraoperative radiation, sequential semi-mega dose therapy followed by PBSCT, immune therapy by the use of CTLs, DCs in the CD34 negative fraction of PBSC. 1) In all 19 children with solid tumor, stem cells necessary for more than two times transplant were harvested, and correlation between age and harvested stem cells was found. 2) In 4 children with solid tumor and 2 healthy donors, the median rate of recovery and purification of CD34 cells was 35.9% and 86.8%, respectively. In neuroblastoma patients, CD34 positive cells necessary
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for more than 5 times transplant were recovered. 3) Purging of contamination of tumor cells by CD34 positive selection was not clarified by test of PGP9.5mRNA real time PCR method and antineuroblastoma monoclonal antibody. 4) In the 4 patients underwent purified CD34 positive stem cell transplant, hematopoietic recovery was as soon as conventional PBSCT. 5) The stem cell recovery rate was negatively correlated with the cryopreservation times, the recovery rate after 2, 3, and 5 years cryopreservation was 74 %, 56 %, and 21 %, respectively. 6) The patient with advanced neuroblastoma who underwent multiple transplant with purified CD34 cells had delayed cellular immune recovery and complicated VZV encephalitis. 7) Cyto-toxic lymphocytes in the PBSC showed the cytotoxic response against K506 and Cos-7.8) Using the dendritic cells concomitantly in the PBSC accelerated the cytotoxic response of CTLs against K506 and Cos-7.9) We designed the total cell therapy for pediatric solid tumors including advanced neuroblastoma. Less
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