© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 23, 1775-1783,
December 5, 2001
© 2001 Oxford University Press
ARTICLE |
Regression of Human T-cell Leukemia Virus Type I (HTLV-I)-Associated Lymphomas in a Rat Model: Peptide-Induced T-Cell Immunity
Affiliations of authors: S. Hanabuchi, T. Ohashi, Y. Koya, H. Kato, A. Hasegawa, F. Takemura, T. Masuda, M. Kannagi, Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Tokyo, and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama, Japan.
Correspondence to: Dr. Mari Kannagi, Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, 1–5-45 Yushima, Bunkyo-Ku, Tokyo 113–8519, Japan (e-mail: kann.impt{at}med.tmd.ac.jp).
Background: Human T-cell leukemia virus type I (HTLV-I) 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-I 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 histocompatibility complex class I molecule, RT1.Al . The cytotoxicity of these lines was directed against the HTLV-I regulatory protein Tax and, specifically, against the epitope, amino acids 180–188 (GAFLTNVPY). 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-I-induced lymphoproliferative disease.
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