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

被引：42

作者：

Hombach, A

Muche, JM

Gerken, M

Gellrich, S

Heuser, C

Pohl, C

Sterry, W

Abken, H

机构：

[1] Univ Cologne, Lab Tumor Genet, Dept Internal Med 1, D-50931 Cologne, Germany

[2] St Elisabeth Krankenhaus Koln Hohenlind, Cologne, Germany

[3] Humboldt Univ, Hosp Charite, Dept Dermatol & Allergy, Berlin, Germany

来源：

GENE THERAPY | 2001年 / 8卷 / 11期

关键词：

cutaneous T cell lymphoma; adoptive immunotherapy; chimeric receptor; CD30;

D O I：

10.1038/sj.gt.3301467

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-V beta7 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.

引用

页码：891 / 895

页数：5

共 19 条

[1] Can combined T-cell- and antibody-based immunotherapy outsmart tumor cells? [J].