A novel cancer immunotherapy with down-regulation of regulatory T cells using pretreatment of mild bone marrow suppression.

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(1) An effect of mild immunosuppression was observed in mice administered cyclophosphamide. Cytotoxic T lymphocyte (CTL) response was enhanced in mice with this pretreatment possibly due to the down regulation of regulatory T cells which is considered to drive T helper-2 (112) immune response.(2) The administration of anti-CD40 ligand monoclonal antibody (mAb) augmented this CTL response.(3) Cancer vaccine protocol using the pretreatment of cyclophosphamide and the administration of a CD40L was evaluated as for its CTL response as well as anti tumor effect. C57B1/6 mice immunized with S11NFEKT peptide using this vaccine protocol were challenged with B16-0UA tumor cell lines. An enhancement of peptide-specific CTL response and anti tumor effect was observed. Its anti tumor effect was strongest in mice immunized with peptide concomitantly given cyclophosphamide and a-CD4OL Although some response was demonstrated in mice immunized with peptide alone, cyclophosphamide and a-CD40L elicited more strong peptide specific CM response and rejected tumor challenged after vaccination.In conclusion, pretreatment of cyclophophamide and a-CD40L aiming at the down regulation of regulatory T cells enhanced peptide specific T cell response and effectively elicited anti tumor response. This vaccine protocol may be the break through for optimal cancer vaccine therapy.