Novel method for in vitro depletion of T cells by monoclonal antibody-targeted photosensitization

被引:11
|
作者
Berki, T [1 ]
Németh, P [1 ]
机构
[1] Univ Pecs, Sch Med, Dept Immunol & Biotechnol, H-7643 Pecs, Hungary
基金
美国国家科学基金会; 匈牙利科学研究基金会;
关键词
immunotargeting; photosensitization; monoclonal antibody conjugate; T lymphocyte; Thy-1;
D O I
10.1016/S0022-1759(97)00201-9
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
An immunotargeting method (called photo-immunotargeting) has been developed for selective in vitro cell destruction. The procedure combines the photosensitizing (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the selective binding ability of monoclonal antibodies (mAb) to cell surface molecules. The photosensitizer HP molecules were covalently attached to monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T lymphocytes, and used for T cell destruction. To increase the selectivity of the conventional targeting methods, a physical activation step (local light irradiation) as a second degree of specificity was employed. The HP in conjugated form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after irradiation at 400 nm, at tenfold lower concentration compared to the photosensitizing effect of unbound HP. The selective killing of T lymphocytes (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a treatment with the phototoxic conjugate and light irradiation. This method can be useful for selective destruction of one population (target cell) in an in vitro heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion to avoid graft vs, host reaction. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:139 / 146
页数:8
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