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The cellular uptake and cytotoxicity of chlorambucil‐monoclonal autibody conjugates
Author(s) -
Smyth Mark J,
Pietersz Geoffrey A,
McKenzie Ian FC
Publication year - 1987
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1987.35
Subject(s) - chlorambucil , chemistry , conjugate , monoclonal antibody , cytotoxicity , biochemistry , stereochemistry , antibody , biology , immunology , in vitro , chemotherapy , mathematical analysis , genetics , mathematics , cyclophosphamide
Summary 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 NH 4 Cl 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.