Inhibition of cancer cell growth by internalized immuno-histone conjugates.
MAb NS 88 directed against breast cancer cells, which is internalized and translocated to the cell nucleus, was conjugated with histone and labeled with 125I. 125I-MAb-histone complexes (M(r) 250,000) were internalized by breast and cervical cancer cells and localized in the cytoplasm and chromatin. Electrophoretic analysis of the cells extracted from the conjugates revealed the same molecular weights of the cytoplasmic and chromatin complexes as those of the native conjugate. Nicotine (0.1%), which suppresses lysosomal degradation, stabilized the conjugates within the cell and prolonged the presence of nondegraded complexes inside the cytoplasm and chromatin from 1 day to at least 3 days. MAb-histone complexes, but not MAb alone, inhibited RNA synthesis and proliferation of cervical and breast cancer cells. A new application of internalized MAbs as the vehicles for protein inhibitors of transcription or replication is discussed.
Rakowicz-Szulczynska
E M
EM
Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha 68198-3255, USA.
McIntosh
D G
DG
Lewis
P
P
Smith
M L
ML
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D002470:Cell Survival / Q000528:radiation effects; D004586:Electrophoresis; D006657:Histones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D009369:Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006657:Histones; D007457:Iodine Radioisotopes