Abstract
To investigate the mode of entry and action of the alkylating agent chlorambucil (CBL), conjugated to monoclonal antibodies (MoAbs), CBL was coupled with three different MoAbs--to the transferrin receptor, to L3T4 and to Ly-2 molecules--and the activity of these conjugates was compared with free CBL. It was clear that CBL and CBL-MoAb conjugates enter cells and are transported differently within the cell prior to their cytotoxic action. Evidence favouring a separate entry point of CBL and CBL-MoAb conjugates is the differential effect of temperature and metabolic inhibitors (2-deoxyglucose and sodium azide) on the processing of both moieties. In addition, the likely sites of cleavage of CBL-MoAb complexes, the lysosomes, were effected by NH4Cl and chloroquine, which inhibited the activity of CBL-MoAb but not free CBL. Thus, it is likely that CBL-MoAb conjugates enter via the antibody binding sites and the CBL is internalised and transported as a passenger.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
