Mechanisms of human CD5 modulation and capping induced by murine monoclonal antibody T101.
We have previously demonstrated that the murine monoclonal antibody T101 induces antigenic modulation when infused into patients with chronic lymphocytic leukemia and cutaneous T-cell lymphoma. In this paper, we extend our studies of T101-induced modulation and compare it to T101-induced capping. We found that, in contrast to antigenic modulation, capping occurred only in the presence of secondary anti-mouse IgG antisera and was altered by drugs that affect the cellular cytoskeleton or energy metabolism. F(ab')2 fragments of T101 induced antigenic modulation with kinetics similar to those of intact T101, but Fab-induced modulation proceeded more slowly and required the continual presence of Fab throughout the incubation. Experiments with radioiodinated T101 demonstrated that initial internalization of the antibody is followed by rapid efflux of intact, immunoreactive T101 from the cells. These data indicate important differences between capping and modulation and suggest that these two phenomena proceed by different mechanisms. More importantly, the data have implications for the potential therapeutic use of monoclonal antibody immunoconjugates.
Shawler
D L
DL
Biotherapeutics, Inc., La Jolla, California 92037.
Johnson
D E
DE
McCallister
T J
TJ
Bartholomew
R M
RM
Dillman
R O
RO
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004705:Endocytosis; D007152:Immunologic Capping / Q000187:drug effects; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000628:therapy; D008562:Membrane Glycoproteins / Q000502:physiology
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D008562:Membrane Glycoproteins; D003571:Cytochalasin B; D003078:Colchicine