IMMUNE-MEDIATED ARREST AND REVERSAL OF ESTABLISHED VISCERAL METASTASES IN ATHYMIC MICE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (10) , 4034-4041
Abstract
The metastasizing MDAY-D2 [mouse sarcoma] tumor of DBA/2 mice disseminates in BALB/c allogeneic athymic nude (nu/nu) mice in a manner identical to that observed in the syngeneic host. The kinetics and organ distribution pattern of metastases from s.c. implants of MDAY-D2 are routinely predictable at any given tumor dose. BALB/c heterozygote (nu/+) litter-mates reject MDAY-D2 grafts because of multiple minor histocompatibility differences that exist between DBA/2 and BALB/c mice. The in vitro cell-mediated cytotoxic response detected in tumor-bearing BALB/c nu/+ mice is low grade (isotope release is .apprx. 40-50% by 24 h 111In-8-hydroxyquinoline assay, .apprx. 6-8% by 6 h 51Cr assay), yet correlates directly with tumor rejection. BALB/c nu/nu mice can be protected against MDAY-D2 by previous reconstitution with lymphoid cells from normal or MDAY-D2-sensitized BALB/c nu/+ mice. Surgically documented, established visceral metastases in BALB/c nu/nu mice can be arrested and regressed by the adoptive transfer of MDAY-D2-sensitized BALB/c nu/+ spleen cells. This represents one of the few models where established metastases have been immunotherapeutically regressed. The MDAY-D2 BALB/c nu/nu mouse model offers unique advantages for studying the role of the immune system in regulating the metastatic process.