In vivo therapeutic effects of interleukin-12 against highly metastatic residual lymphoma

David J. Verbik, Warren W. Stinson, Michael J. Brunda, Anne Kessinger, Shantaram S. Joshi

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25 Scopus citations

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 μg/mouse) showed that a 0.35 μg 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 μg/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 α-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.

Original languageEnglish (US)
Pages (from-to)219-229
Number of pages11
JournalClinical and Experimental Metastasis
Volume14
Issue number3
StatePublished - Aug 7 1996

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Keywords

  • Antitumor effects
  • Immune augmentation
  • Interleukin-12
  • Residual lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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