Immunotherapy of leukemias by targeting hematopoietic lineage-specific minor histocompatibility antigens
| Project/Area Number |
13671092
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
AKATSUKA Yoshiki Aichi Cancer Center Division of Immunology, Senior Researcher, 腫瘍免疫学部, 主任研究員 (70333391)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toshitada Aichi Cancer Center Research Institute, Director, 研究所, 所長 (00124529)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Minor histocompatibility antigen / Cytotoxic T lymphocyte / Adoptive immunotherapy / Leukemia / 細胞障害性T細胞 / マイナー組織適合性抗原 |
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| Research Abstract |
Cytotoxic T lymphocytes (CTL) specific for minor histocompatibility antigens (mHAgs) whose tissue expression is limited to hematopoietic cells are useful for immunotherapy of relapsed leukemia following allogeneic hematopoietic cell transplantation (HCT). We have obtained peripheral blood samples from 26 patients receiving HCT during the research period and attempted to generate CTL restricted by HLA-A24, the most common HLA in Japanese. To facilitate the procedure, we devised a novel method to screen for the presence of mHAgs-specific CTL restricted by HLA of interest in CTL lines by using HLA transfected B lymphoblastoid cell lines retrovirally and interferon-gamma release-based assays. We successfully generated 4 distinct HLA-A24-restricted CTL clones. By using LCL from members of large CEPH families whose genetic markers had been typed in combination with linkage analysis, gene(s) encoding mHAgs detectable 2 distinct CTL restricted by HLA-A24 and B44 were located at chromosome 15q24.5. Of 39 genes within the region, we determined the gene encoding the mHAgs using various online databases (dbSNP, SAGE, UCSC Human Genome Browser) and softwares (BIMAS). The gene, BCL2A1, possesses three single nucleotide polymorphisms, two of which turned out to encode two mHAgs epitopes detected by the 2 CTL clones used. BCL2A1 is expressed in only hematopoietic cells, thus is thought to be a good candidate for immunotherapy of leukemia. We have successfully induced CTL lines specific for the BCL2A1 mHAg using peptide-pulsed antigen presenting cells. We plan on conducting a phase I clinical study of adoptive immunotherapy for patients with relapsed leukemia following allogeneic HCT using ex vivo expanded CTL clones specific for the BCL2A1 mHAgs.
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Report
(3 results)
Research Products
(17 results)
