Regression of human T-cell leukemia virus type I (HTLV-I)-associated lymphomas in a rat model: Peptide-induced T-cell immunity

被引:55
作者
Hanabuchi, S [1 ]
Ohashi, T [1 ]
Koya, Y [1 ]
Kato, H [1 ]
Hasegawa, A [1 ]
Takemura, F [1 ]
Masuda, T [1 ]
Kannagi, M [1 ]
机构
[1] Tokyo Med & Dent Univ, Div Med Res, Dept Immunotherapeut, Bunkyo Ku, Tokyo 1138519, Japan
关键词
D O I
10.1093/jnci/93.23.1775
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Human T-cell leukemia virus type I (HTLV-1) is etiologically linked to adult T-cell leukemia (ATL). The disease has a high mortality rate and is resistant to chemotherapy; therefore, immunologic approaches to treatment could be of interest. We have previously shown that athymic rats inoculated with a syngeneic (i.e., with the same genetic background) HTLV-I-infected T-cell line (FPM1-V1AX) develop ATL-like disease and that the transfer of T cells from normal syngeneic rats immunized with FPM1-V1AX cells prevents disease development. In this study, we further characterized the host antitumor immunity to explore the possibility of peptide-based vaccination against the ATL-like disease. Methods: Immune T cells from rats immunized with FPM1-V1AX cells were analyzed for their phenotypes and cytotoxic properties. The epitope recognized by the T cells was analyzed by fine mapping. To evaluate the antitumor effects of a peptide-based vaccine, normal rats were immunized with synthetic oligopeptides corresponding to the epitope, the T cells were transferred to athymic rats inoculated with HTLV-1 infected cells, and tumor size was monitored. Results: Both CD4(+) and CD8(+) T-cell populations from rats immunized with FPM1-V1AX cells inhibited the growth of FPM1-V1AX cell-induced lymphomas in vivo. Long-term culture of splenic T cells from the immunized rats repeatedly resulted in establishment of CD8(+) HTLV-I-specific cytotoxic T lymphocyte (CTL) lines restricted to the rat major histo compatibility complex class I molecule, RT1.A(1). The cytotoxicity of these lines was directed against the HTLV-1 regulatory protein Tax and, specifically, against the epitope, amino acids 180-188 (GAFLT-NVPY). Adoptive transfer of the Tax 180-188-specific CTL line or freshly prepared T cells from rats vaccinated with the Tax 180-188 oligopeptide prevented the development of FPM1-V1AX-cell induced lymphomas in athymic rats in comparison with control groups (two rats in each group). Conclusions: This study indicated a potential therapeutic effect of peptide-based vaccination against HTLV-1-induced lymphoproliferative disease.
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页码:1775 / 1783
页数:9
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