CD3X anti-nitrophenyl bispecific diabodies: universal immunotherapeutic tools for retargeting T cells to tumors.
We developed a universal recombinant bispecific molecule (BiMol) that is capable of redirecting cytotoxic T cells to tumor cells via tagged anti-tumor ligands such as antibody fragments or cytokines. A recombinant bispecific diabody with binding specificities for the CD3 molecule on T cells as well as for the hapten nitrophenyl (NIP) was produced. This bispecific molecule is capable of redirecting cytotoxic T cells to kill a series of malignant cells, including B cell lymphoma, Hodgkin's lymphoma, and colon carcinoma via NIP-conjugated ligands to tumor-associated antigens. Cytotoxic activity of the diabody was found to be comparable to tetradoma-derived bispecific antibodies with similar specificities. Our findings demonstrate that universal CD3xanti-NIP diabodies could be used for T cell based cellular immunotherapy in a variety of human malignancies. Additionally, these bispecific molecules allow fast and economic testing of tumor-associated antigens on malignant cells for their potential use as immunotherapeutic target structures if corresponding hapten-conjugated antibodies or ligands are available.
Manzke
O
O
Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Fitzgerald
K J
KJ
Holliger
P
P
Klock
J
J
Span
M
M
Fleischmann
B
B
Hescheler
J
J
Qinghua
L
L
Johnson
K S
KS
Diehl
V
V
Hoogenboom
H R
HR
Bohlen
H
H
D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006241:Haptens / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D019169:Jurkat Cells; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D006241:Haptens; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D002118:Calcium