Generation of Fas-independent CD4+ cytotoxic T-cell clone specific for p190 minor bcr-abl fusion peptide

Tanaka, Yuji; Takahashi, Tsuyoshi; Nieda, Mie; Masuda, Shigeo; Kashiwase, Koichi; Takahashi, Tokiharu; Ogawa, Seishi; Chiba, Shigeru; Juji, Takeo; Hirai, Hisamaru

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Volume 26, Issue 3 , Pages 317-321, March 2002

Generation of Fas-independent CD4+ cytotoxic T-cell clone specific for p190 minor bcr-abl fusion peptide

Yuji Tanaka
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
Tsuyoshi Takahashi
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
Mie Nieda
- The Japan Red Cross Central Blood Center, Tokyo, Japan
Shigeo Masuda
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
Koichi Kashiwase
- The Japan Red Cross Central Blood Center, Tokyo, Japan
Tokiharu Takahashi
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
Seishi Ogawa
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
Shigeru Chiba
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
Takeo Juji
- The Japan Red Cross Central Blood Center, Tokyo, Japan
Hisamaru Hirai
- Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
- Corresponding author. Present address: Department of Cell Therapy and Transplantation Medicine, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. Tel.: +81-3-3815-5411x35600; fax: +81-3-5689-7286

Received 19 February 2001; accepted 26 June 2001.

Abstract

In the majority of Ph+ALL patients, p190 bcr-abl fusion protein is generated in the Philadelphia chromosome. The fusion protein may serve as a leukemia antigen because it is not expressed in normal cells and hardly in any other malignancy. From a healthy donor, we have established a p190 bcr-abl fusion peptide-specific CD4+ cytotoxic T-cell clone, activation of which depends on HLA-DRB1*1501. This T-cell clone has a strong cytotoxic activity against autologus MoDCs pulsed with e1a2 peptide and its cytotoxicity is not mediated by Fas/Fas ligand or perforin pathway. Success in establishment of the p190 bcr-abl fusion peptide-specific T-cell clone encourages us to develop a new approach to an effective immunotherapy for Ph+ALL.

Keywords: Philadelphia chromosome-positive acute lymphoblastic leukemia, Minor BCR/ABL, CTL