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 I-125. I-125-MAb-histone complexes (M(r) 250,000) were in ternalized by breast and cervical cancer cells and localized in the cy toplasm and chromatin. Electrophoretic analysis of the cells extracted from the conjugates revealed the same molecular weights of the cytopl asmic and chromatin complexes as those of the native conjugate. Nicoti ne (0.1%), which suppresses lysosomal degradation, stabilized the conj ugates within the cell and prolonged the presence of nondegraded compl exes 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 transcr iption or replication is discussed.