PERFORMANCE OF CD3XCD19 BISPECIFIC MONOCLONAL-ANTIBODIES IN B-CELL MALIGNANCY

被引:14
作者
HAAGEN, IA
机构
[1] Department of Immunology, University Hospital, Utrecht
关键词
IMMUNOTHERAPY; BISPECIFIC ANTIBODIES; B CELL MALIGNANCY; T CELL ACTIVATION;
D O I
10.3109/10428199509112195
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bispecific monoclonal antibodies, with a dual specificity for tumor associated antigens on target cells and for surface markers on immune effector cells, have been shown (in vitro) to be effective in directing and triggering effector cells to kill target cells resulting in target cell lysis. Bispecific monoclonal antibodies (BsAb) against the CD3 antigen on T cells and the CD19 antigen on B cell were developed. Data obtained by in vitro experiments might indicate that clinical responses in BsAb immunotherapy, will only be obtained in patients with minimal tumor load and may need additional T cell stimulation via cytokines such as IL-2. Although these experiments have shown us their limitations, they also include the promise of BsAb-directed immunotherapy in B cell malignancy as further demonstrated during a Phase I trail, showing little toxicity. Clearly, much remains to be done before this BsAb is routinely used for therapy, but, the results presented show that the CD3xCD19 BsAb has a potential as a therapeutic agent in B cell malignancy. This report describes the experiments performed to test a new immunotherapeutic approach for the treatment of B cell malignancy. Bispecific antibodies are described that can target cytotoxic T cells to tumor cells and elicit a cytolytic action towards these cancer cells.
引用
收藏
页码:381 / 393
页数:13
相关论文
共 161 条
[61]  
Friend P.J., Immunosuppression with monoclonal antibodies, Curr. Opin. Immunol., 2, pp. 859-863, (1990)
[62]  
Stamenkovic I., Seed B., CD 19, the earliest differentiation antigen of the B cell lineage, bears three extracellular immunoglobulin-like domains and an Epstein-Barr virus-related cytoplasmic tail, J. Exp. Med., 168, pp. 1205-1210, (1988)
[63]  
Zhou L.J., Ord D.C., Hughes A.L., Tedder T.F., Structure and domain organization of the CD 19 antigen of human, mouse, and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain, J. Immunol., 147, pp. 1424-1432, (1991)
[64]  
Bradbury L.E., Kansas G.S., Levy S., Evans R.L., Tedder T.F., The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-I and Leu-13 molecules, J. Immunol., 149, pp. 2841-2850, (1992)
[65]  
De Rie M.A., Schumacher T.N.M., van Schijndel G.M.W., van Lier R.A.W., Miedema F., Regulatory role of CD19 molecules in B-cell activation and differentiation, Cell. Immunol., 118, pp. 368-381, (1989)
[66]  
Rigley K.P., Callard R.E., Inhibition of B cell proliferation with anti-CD19 monoclonal antibodies: anti-CD19 antibodies do not interfere with early signaling events triggered by anti-IgM or interleukin, Eur. J. Immunol., 21, pp. 535-540, (1991)
[67]  
Carter R.H., Fearon D.T., CD19: lowering the tresh-old for antigen receptor stimulation of B lymphocytes, Science, 256, pp. 105-107, (1992)
[68]  
Ghetie M.A., Picker L.J., Richardson J.A., Tucker K., Uhr J.W., Vitetta E.S., Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest, Blood, 83, pp. 1329-1336, (1994)
[69]  
Uckun F.M., Ledbetter J.A., Immunobiologic differences between normal and leukemic human B-cell precursors, Proc. Natl. Acad. Sci. USA, 85, pp. 8603-8607, (1988)
[70]  
Uckun F.M., Regulation of human B-cell ontogeny, Blood, 76, pp. 1908-1923, (1990)