Effector cell analysis of human multidrug-resistant cell killing by mouse-human chimeric antibody against P-glycoprotein.
A mouse-human chimeric monoclonal antibody (mAb), MH162, against P-glycoprotein was previously found to be more effective than an all-mouse mAb (MRK16) in lysis of multidrug-resistant (MDR) tumor cells by blood mononuclear cells. The present study was performed to identify the effector cells responsible for the chimeric mAb-dependent cell-mediated cytotoxicity (ADCC) against MDR cells. The ADCC reaction was assessed by a 6-h 51Cr release assay. Highly purified lymphocytes (greater than 99%), monocytes (greater than 99%) and neutrophils (greater than 96%) were obtained from peripheral blood of the same healthy donors. A comparison of these three effector cell populations showed no difference between MH162 and its all-murine counterpart MRK16 in MDR cell lysis by monocytes or neutrophils. But MH162 was more effective than MRK16 in lymphocyte-mediated lysis of the MDR cells. The lymphocytes responsible for this ADCC had CD16+ Fc receptors. Pretreatment of monocytes with colony-stimulating factors (IL-3, GM-CSF and M-CSF) caused significant increase in their MH162-mediated lysis of MDR cells. Another anti-P-glycoprotein chimeric mAb (MH171) was also more effective than its murine counterpart MRK17 in lymphocyte-mediated lysis of MDR cells. These findings suggest that mouse-human chimeric mAbs may be useful therapeutically for in vivo destruction of MDR cancer cells by the ADCC reaction.
Third Department of Internal Medicine, University of Tokushima School of Medicine.
Y
Y
Nishioka
S
S
Sone
Y
Y
Heike
H
H
Hamada
K
K
Ariyoshi
T
T
Tsuruo
T
T
Ogura
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011993:Recombinant Fusion Proteins; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins