Related Experiment Videos
Effector characteristics of the IgG3 murine monoclonal antibody 113F1
L M Weiner1, C M Zarou, J O'Brien
1Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Successful immunotherapy with unconjugated murine monoclonal antibodies (MAbs) is likely to require antibodies with potent effector characteristics such as antibody-dependent cellular cytotoxicity (ADCC). The newly developed IgG3 isotype antibody, 113F1, binds to a target antigen present in high copy number on SK-Br-3 cell surfaces. 113F1 does not appear to participate in complement-mediated cytotoxicity, but is a potent mediator of ADCC by human monocytes directed against a variety of malignant cell lines expressing 113F1's target antigen. Although recombinant interleukin-2 (rIL-2) promotes nonspecific monocyte cytotoxicity, preincubation with this cytokine has no effect on monocyte ADCC in our system. 113F1 promotes ADCC by nonadherent cells expressing lymphokine-activated killer (LAK) activity following incubation of these cells in rIL-2. These latter effects are abrogated by Fc receptor blockade prior to addition of 113F1. 113F1 is a more potent mediator of ADCC by monocytes or LAK cells than is 17-1A, an extensively tested unconjugated murine IgG2a isotope MAb. These data suggest that unconjugated 113F1 MAb immunotherapy trials should investigate treatment with the MAb alone. In addition, 113F1 could be administered with rIL-2, either alone or supplemented with infusions of autologous LAK cells.
Successful immunotherapy with unconjugated murine monoclonal antibodies (MAbs) is likely to require antibodies with potent effector characteristics such as antibody-dependent cellular cytotoxicity (ADCC). The newly developed IgG3 isotype antibody, 113F1, binds to a target antigen present in high copy number on SK-Br-3 cell surfaces. 113F1 does not appear to participate in complement-mediated cytotoxicity, but is a potent mediator of ADCC by human monocytes directed against a variety of malignant cell lines expressing 113F1's target antigen. Although recombinant interleukin-2 (rIL-2) promotes nonspecific monocyte cytotoxicity, preincubation with this cytokine has no effect on monocyte ADCC in our system. 113F1 promotes ADCC by nonadherent cells expressing lymphokine-activated killer (LAK) activity following incubation of these cells in rIL-2. These latter effects are abrogated by Fc receptor blockade prior to addition of 113F1. 113F1 is a more potent mediator of ADCC by monocytes or LAK cells than is 17-1A, an extensively tested unconjugated murine IgG2a isotope MAb. These data suggest that unconjugated 113F1 MAb immunotherapy trials should investigate treatment with the MAb alone. In addition, 113F1 could be administered with rIL-2, either alone or supplemented with infusions of autologous LAK cells.