Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody.
An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr-labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.
Oshimi
K
K
Department of Medicine, Tokyo Women's Medical College, Japan.
Seto
T
T
Oshimi
Y
Y
Masuda
M
M
Okumura
K
K
Mizoguchi
H
H
D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008213:Lymphocyte Activation; D015260:Neprilysin; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015260:Neprilysin