Immune regulation of 5T2 mouse multiple myeloma. II. Immunological treatment of 5T2 MM residual disease.

The transplantable murine 5T2 multiple myeloma (MM) has been shown to be sensitive to idiotype-specific immunity, provided the recipient mice were immunized before transplantation. In the present study, anti-idiotype treatment was initiated after inoculation of the mice with 5T2 MM cells. Since in MM the serum idiotype concentration is far too high for anti-idiotype antibodies to reach the target cells, reduction of the MM to a minimal residual disease should be performed before. Intravenous (i.v.) or intraperitoneal (i.p.) administration of allogeneic (BALB/c) monoclonal anti-5T2 MM idiotype antibodies 3 days after i.v. infusion of the 5T2 MM cells into the mice, i.e. before 5T2 MM idiotype was serologically detectable, prevented the development of 5T2 MM in the majority of the animals. All mice that had not been treated with the anti-idiotype antibody became seropositive for 5T2 MM idiotype after 6 weeks. When mice with clearly developed 5T2 MM were treated with cyclophosphamide in order to obtain substantial tumor reduction, subsequent i.v. treatment with anti-5T2 MM idiotype antibodies resulted in prevention of myeloma growth in most animals. Injection of the antibody i.p. was, however, less effective. All mice that had been treated with cyclophosphamide only became seropositive for 5T2 MM and died. The results of these experiments demonstrated that passive anti-idiotype treatment of 5T2 MM is successful if the tumor mass is very small. The effector mechanisms of this treatment has to be investigated.