Biomaterial Database

The cellular uptake and cytotoxicity of chlorambucil-monoclonal antibody conjugates. 1987

M J Smyth, and G A Pietersz, and I F McKenzie

Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.

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.

UI	MeSH Term	Description	Entries
D002699	Chlorambucil	A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)	4-(Bis(2-chloroethyl)amino)benzenebutanoic Acid,Amboclorin,CB-1348,Chloraminophene,Chlorbutin,Leukeran,Lympholysin,N,N-Di-(2-chloroethyl)-p-aminophenylbutyric Acid,NSC-3088,CB 1348,CB1348,NSC 3088,NSC3088
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000963	Antimetabolites	Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)	Antimetabolite
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus