IN-VIVO THERAPEUTIC EFFECTS OF INTERLEUKIN-12 AGAINST HIGHLY METASTATIC RESIDUAL LYMPHOMA

Despite considerable advancement in anticancer therapy, minimal residu al disease (MRD) is still a major problem in the clinical management o f cancer, including lymphoma, In this report, we have studied the anti tumor effects of interleukin-12 (IL-12) against an aggressive liver me tastatic murine RAW117-H10 lymphoma. Our results using three different doses of IL-12 (0.175, 0.35 and 0.7 mu g/mouse) showed that a 0.35 mu g dose is the most efficacious against lymphoma grown in intact mice. Furthermore, we have evaluated the therapeutic effects of IL-12 again st residual lymphoma in a transplantation setting. BALB/c mice were tr eated with high-dose therapy (HDT) and transplanted with syngeneic bon e marrow cells added with a known number of RAW117-H10 lymphoma cells to mimic the clinical situation of MRD. The mice were then treated wit h IL-12 (0.25 mu g/mouse/day) alone or IL-12 plus activated cytotoxic effector cells, Our results showed that IL-12 had a significant (P<0.0 5) antitumor therapeutic effect against liver metastatic lymphoma grow n in intact mice as well as in lymphoma-bearing mice treated with HDT followed by stem cell transplantation as determined by survival period . The therapeutic effect of IL-12 was also demonstrated by a very sign ificant decrease (P<0.05) in the tumor burden in livers from the IL-12 -treated mice. Mice that were treated with IL-12 following HDT and hem atopoietic stem cell transplantation had a significant decrease in cir culating white blood cells (P<0.05), a significant increase in spleen weight and cellularity (P<0.05), and hematopoietic progenitor cells (P <0.05), a significant increase in the number of splenocytes expressing IL-2 alpha-chain receptor (P<0.05), and an increase in the frequency of natural killer cells in their spleens, These studies suggest that c ytokines such as IL-12 may have the potential to mediate antitumor eff ects against residual lymphoma without compromising lymphohematopoieti c recovery.