[Bi-specific F(ab')2 enhances cytolytic activities of LAK cells against human small cell lung cancer (SCLC)].
In order to enhance cytolytic activity of lymphokine activated killer (LAK) cells against human small cell lung cancer (SCLC), bispecific F(ab')2 was used with human LAK cells and human SCLC cell lines (i.e. N231 and H69) as targets. For the construction of bispecific F(ab')2, LU246 monoclonal antibody (mAb) recognizing the antigen expressed on the surface of both SCLC cell lines, was employed. OKT3 or 3G8 mAbs recognizing CD3 on T cell and CD16 on NK cell functional molecules respectively, were chemically cross-linked to LU246 mAb using 5,5'-dithio-bis 2-nitrobenzoic acid (DTNB). Bispecific F(ab')2 adding to LAK cells increased the conjugation with target cells. The phenotypes of LAK cells change at their various culture times. Although cytolytic activity of LAK cells gradually decreases after one week of culture time, the enhanced cytotoxicity of LAK cell using bispecific F(ab')2 has been kept even after long culture. Furthermore, target cell lysis enhanced by bispecific F(ab')2 has been greater than that by classical ADCC using LU246 mAb. These bispecific antibodies should be effective reagents for adoptive immunotherapy in human SCLC patients.
Azuma
A
A
Department of Pulmonary Disease, Nippon Medical School.
Niitani
H
H
D000918:Antibody Specificity; D018288:Carcinoma, Small Cell / Q000276:immunology*; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007376:Interleukin-2 / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2