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- Title
Regression of human T-cell leukemia virus type I (HTLV-I)-associated lymphomas in a rat model: peptide-induced T-cell immunity.
- Authors
Hanabuchi, Shino; Ohashi, Takashi; Koya, Yoshihiro; Kato, Hirotomo; Hasegawa, Atsuhiko; Takemura, Fumiyo; Masuda, Takao; Kannagi, Mari; Hanabuchi, S; Ohashi, T; Koya, Y; Kato, H; Hasegawa, A; Takemura, F; Masuda, T; Kannagi, M
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.A(l). 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).<bold>Conclusions: </bold>This study indicated a potential therapeutic effect of peptide-based vaccination against HTLV-I-induced lymphoproliferative disease.
- Subjects
HTLV-I; VACCINATION; OLIGOPEPTIDES; LYMPHOMA treatment; METABOLISM in viruses; AMINO acids; ANIMAL experimentation; ANTIGENS; CELL lines; COMPARATIVE studies; GENES; IMMUNIZATION; IMMUNOLOGY technique; LYMPHOCYTIC leukemia; LYMPHOMAS; LYMPHOPROLIFERATIVE disorders; RESEARCH methodology; MEDICAL cooperation; MICE; MONOCLONAL antibodies; PEPTIDES; RATS; RESEARCH; RETROVIRUSES; T cells; TIME; VACCINES; PHENOTYPES; CANCER vaccines; EVALUATION research; CANCER cell culture
- Publication
JNCI: Journal of the National Cancer Institute, 2001, Vol 93, Issue 23, p1775
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/93.23.1775