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T cells can be directed to antigen-specific, MHC-independent target ceil lysis by grafting with a recombinant receptor with antibody-like specificity. Here, we asked whether T cells from the peripheral blood of a patient with cutaneous T cell lymphoma can be recruited for an immune response against autologous tumor cells. Lymphoma cells with a CD3[sup -] CD4[sup +] CD30[sup +] phenotype and clonal TCR-Vβ7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3[sup +] CD25[sup +] activated normal T cells despite ongoing tumor progression. Peripheral blood-derived T cells from the lymphoma patient were retrovirally engrafted with a recombinant anti-CD30scFv-γ receptor. Upon cocultivation with autologous CD30[sup +] lymphoma cells, grafted T cells increase IFN-γ secretion and lyse specifically lymphoma cells with high efficiency, even at an effector to target cell ratio of as low as 1:20. Our data demonstrate that the recombinant anti-CD30-γ receptor overcomes T cell tolerance for tumor cells and directs T cells specifically against autologous lymphoma cells. [ABSTRACT FROM AUTHOR]