T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30(+) cutaneous lymphoma cells

T cells can be directed to antigen-specific, MHC-independent target cell ly sis 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(-) CD4(+) CD30(+) phenoty pe and clonal TCR-V beta7 rearrangement were isolated from a cutaneous lesi on. The lymphoma lesion additionally harbored CD3(+) CD25(+) activated norm al T cells despite ongoing tumor progression. Peripheral blood-derived T ce lls from the lymphoma patient were retrovirally engrafted with a recombinan t anti-CD30-scFv-gamma receptor. Upon cocultivation with autologous CD30(+) lymphoma cells, grafted T cells increase IFN-gamma secretion and lyse spec ifically 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 an ti-CD30-gamma receptor overcomes T cell tolerance for tumor cells and direc ts T cells specifically against autologous lymphoma cells.