Induction of cytotoxicity in human T cells coated with anti-glioma × anti-CD3 bispecific antibody against human glioma cells

Abstract

✓ A bifunctional hetero-F(ab′)2 antibody fragment was developed that contained the Fab portions from anti-CD3 and anti-glioma monoclonal antibodies. The antibody simultaneously recognized two different molecules, the CD3 complex on effector T cells and a human glioma-associated antigen; thus, it could cross-link effector and target cells. This bispecific F(ab′)2 fragment induced peripheral blood mononuclear cells (PBMC's) from healthy donors to lyse cells of the human glioma cell line, U251MG, which are resistant to natural killer cell-mediated cytolysis. The effect of the bispecific antibody on lymphokine-activated killer (LAK) cell activity was tested in patients suffering from malignant glioma. For this study, PBMC's from these patients were preactivated with recombinant interleukin-2 and their killer activity against U251MG cells was investigated in vitro with and without the bispecific antibody. The LAK cell activity of the PBMC's from patients with malignant gliomas was found to be suppressed compared with those of healthy donors. However, after preincubation with bispecific antibody, the patients' LAK cells exhibited marked cytolytic activity against U251MG cells. These findings suggest that this bispecific antibody may be a useful addition to anti-glioma immunotherapy.