Cis-diamminedichloroplatinum (II) (cis-DDP) and its structural analogue
cis-diamminediaquoplatinum(II) nitrate (
cis-aq) were complexed via an intermediate
dextran carrier to
antibodies specifically reactive with B
lymphoma cells (38C-13). The potential use of these drugs in site-directed immunotargeting was evaluated. The two
platinum(II) compounds were previously shown to form pharmacologically active complexes with
carboxymethyl dextran (CM-dex). For the purpose of preparing
drug-antibody complexes, CM-dex was first conjugated to idiotypic
antibodies that recognize a specific membrane
IgM on the B
lymphoma cells. The conjugates were prepared by a modified water-soluble
carbodiimide method in which
N-hydroxysuccinimide was used to enhance the coupling reaction. The conjugation was followed by separation of the CM-dex-
IgG conjugates from unconjugated CM-dex or
IgG. The
platinum(II) compounds were then complexed to the CM-dex-
IgG resulting in complexes carrying up to 50 mole
drug/mole
IgG. Both cis-DDP and
cis-aq complexes of CM-dex-antibody conjugates maintained most of the original cell-binding activity of the
antibodies. An in vitro assay was used to demonstrate selective binding to
tumor cells in which the target cells were treated with specific
immune complexes and washed before culture. In this assay the specific complexes showed preferential cytotoxicity for the B
lymphoma cells in comparison to the free drugs,
drug CM-dex, or nonspecific
immune complexes.