title: In vivo therapeutic effects of interleukin-12 against highly metastatic residual lymphoma.
abstract: Despite considerable advancement in anticancer therapy, minimal residual disease (MRD) is still a major problem in the clinical management of cancer, including lymphoma. In this report, we have studied the antitumor effects of interleukin-12 (IL-12) against an aggressive liver metastatic murine RAW117-H10 lymphoma. Our results using three different doses of IL-12 (0.175, 0.35 and 0.7 micrograms/mouse) showed that a 0.35 micrograms dose is the most efficacious against lymphoma grown in intact mice. Furthermore, we have evaluated the therapeutic effects of IL-12 against residual lymphoma in a transplantation setting. BALB/c mice were treated with high-dose therapy (HDT) and transplanted with syngeneic bone marrow cells added with a known number of RAW117-H10 lymphoma cells to mimic the clinical situation of MRD. The mice were then treated with IL-12 (0.25 micrograms/mouse/day) alone or IL-12 plus activated cytotoxic effector cells. Our results showed that IL-12 had a significant (P < 0.05) antitumor therapeutic effect against liver metastatic lymphoma grown 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 significant 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 hematopoietic stem cell transplantation had a significant decrease in circulating 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 cytokines such as IL-12 may have the potential to mediate antitumor effects against residual lymphoma without compromising lymphohematopoietic recovery.
authors.affiliation: Department of Cell Biology, University of Nebraska Medical Center, Omaha, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Verbik
authors.forename: W W
authors.initials: WW
authors.lastname: Stinson
authors.forename: M J
authors.initials: MJ
authors.lastname: Brunda
authors.forename: A
authors.initials: A
authors.lastname: Kessinger
authors.forename: S S
authors.initials: SS
authors.lastname: Joshi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D005260:Female; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D008223:Lymphoma / Q000188:drug therapy* / Q000628:therapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000401:mortality; D009929:Organ Size; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013234:Stem Cells; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D018664:Interleukin-12