Regulation of serum antibodies induced in syngeneic rats after administration of monoclonal antibody MT10:21.

Monoclonal antibody (mAb) MT10:21, a rat IgG2a, reacts with antigens expressed on the metastatic subclone MTLn3 of the 13762NF rat mammary adrenocarcinoma (North, Steck & Nicolson, 1986). The clearance of mAb MT10:21 from circulation was monitored 15 days after s.c. injection of MTLn3 tumour cells into the mammary fat pad of syngeneic rats. At this point, when tumour-burden was small (< 1 cm average diameter), mAb MT10:21 was injected i.v. and serum samples were taken over the 7 days following injection. It was observed that when mAb MT10:21 was injected i.v. into syngeneic rats it induced a humoral immune response. Four days after injection of mAb, IgM serum antibodies which bound to the MTLn3 cell line were detected in both tumour and non-tumour bearing rats. Using a binding assay, tumour-bearer sera showed a steady increase in MTLn3-reactive antibodies over the 7-day assay period. These MTLn3-reactive antibodies were detectable in non-tumour-bearer sera, but reactivity was not as pronounced. Tumour-bearing rats also had serum IgM antibodies which bound to mAb MT10:21 in vitro, but not to a non-specific, isotype-identical control mAb, MC9:13. These serum antibodies were able to partially inhibit (up to 47%) the binding of 125I-labelled mAb MT10:21 to MTLn3 cells. This anti-idiotypic immune response was not observed in the non-tumour bearers. When the tumour was allowed to grow for a period of 30 days in vivo (average tumour diameter 2 cm), these serum antibodies were not readily detectable, suggesting that tumour burden had a significant effect on suppressing the humoral immune responsiveness of these tumour-bearing rats. In a standard delayed-type hypersensitivity (DTH) assay specific immunity to mAb MT10:21 was induced in vivo.