Augmentation by bispecific F(ab')2 reactive with P-glycoprotein and CD3 of cytotoxicity of human effector cells on P-glycoprotein positive human renal cancer cells.
A bispecific F(ba')2 was constructed that was composed of two Fab fragments, one derived from anti-CD3 monoclonal antibody (mAb) (OKT3) and the other from anti P-glycoprotein mAb (MRK 16). This bispecific F(ab')2 enhanced the binding and cytotoxicity of human peripheral blood mononuclear cells (PBMCs) on P-glycoprotein-positive human kidney cancer cells (ADMHK/E). It had no effect on the cytotoxicity of PBMCs on P-glycoprotein-negative HK/E cells [long-term cultured HK/E (LCHK/E)]. Control F(ab')2 composed of OKT3 or MRK16 alone did not influence the cytotoxicity of PBMCs on ADMHK/E cells. These findings suggest that the MRK16-OKT3 bispecific F(ab')2 may be therapeutically beneficial in treatment of human multidrug-resistant cancers.
Third Department of Internal Medicine, University of Tokushima, School of Medicine.
Y
Y
Heike
K
K
Okumura
T
T
Tsuruo
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000915:Antibody Affinity; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex; D002292:Carcinoma, Renal Cell; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D004317:Doxorubicin