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 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(-) CD4(+) CD30(+) phenotype and clonal TCR-Vbeta7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3(+) CD25(+) activated normal T cells despite ongoing tumor progression. Peripheral blood-derived T cells from the lymphoma patient were retrovirally engrafted with a recombinant anti-CD30-scFv-gamma receptor. Upon cocultivation with autologous CD30(+)lymphoma cells, grafted T cells increase IFN-gamma 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-gamma receptor overcomes T cell tolerance for tumor cells and directs T cells specifically against autologous lymphoma cells.
Hombach
A
A
Department I of Internal Medicine, Laboratory Tumor Genetics, University of Cologne, Germany.
Muche
J M
JM
Gerken
M
M
Gellrich
S
S
Heuser
C
C
Pohl
C
C
Sterry
W
W
Abken
H
H
D000328:Adult; D002469:Cell Separation; D018920:Coculture Techniques; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D017730:Ki-1 Antigen; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000628:therapy*; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
D017730:Ki-1 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins