Induction of tumor-cell lysis by bi-specific antibody recognizing ganglioside GD2 and T-cell antigen CD3.
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 antibody-heteroconjugate 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.
I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany.
H
H
Bernhard
J
J
Karbach
W
W
Strittmatter
K H
KH
Meyer zum Büschenfelde
A
A
Knuth
D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D003110:Colonic Neoplasms / Q000628:therapy; D003429:Cross Reactions / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D017252:CD3 Complex; D005732:Gangliosides; D007074:Immunoglobulin G; C019403:ganglioside, GD2