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Induction of tumor-cell lysis by bi-specific antibody recognizing ganglioside GD2 and T-cell antigen CD3

✍ Scribed by Helga Bernhard; Julia Karbach; Karl-Hermann Meyer Zum Büschenfelde; Wolfgang Strittmatter; Alexander Knuth

Publisher
John Wiley and Sons
Year
1993
Tongue
French
Weight
589 KB
Volume
55
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

Human tumor cells expressing ganglioside GD2 were lysed by various effector populations targeted with an anti‐CD3‐anti‐GD2 bi‐specific antibody (BAb CD3 x GD2). This antibodyheteroconjugate was prepared by chemically cross‐linking the OKT‐3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes with the ganglioside MAb ME 361, which binds preferentially to the tumor‐associated ganglioside GD2. The specificity of target‐cell lysis by the cytotoxic T cells (CTL) was mediated by the specificity of the targeting antibody: GD2‐negative cells were not lysed in the presence of the CD3 x GD2 BAb. A dose‐dependent response was observed in a range of 10 to 10,000 ng/ml. In contrast, 2 other BAbs recognizing the tumor‐associated antigens EGF‐R and TKB‐2 had greater potency to mediate tumor‐cell lysis than the GD2 x CD3 BAb. Peripheral‐blood cells (PBL) stimulated with OKT‐3 MAb or with irradiated tumor cells in a mixed lymphocyte culture (MLTC) could be induced to lyse GD2‐positive tumor cells in the presence of CD3 x GD2 BAb. The tumor‐cell lysis could be mediated by autologous or allogeneic effector cells. NK cells had no influence on the BAb‐induced cytotoxicity.

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