Synergistic effect of Nocardia rubra cell wall skeleton and recombinant interleukin 2 for in vivo induction of lymphokine-activated killer cells

Cancer Res. 1991 Oct 1;51(19):5261-5.

Abstract

C57BL/6 mice inoculated i.p. with 3LL tumor cells were treated by local combination therapy with Nocardia rubra cell wall skeleton (N-CWS) and recombinant interleukin 2 (rIL-2). The combination treatment significantly prolonged their survival and augmented lymphokine-activated killer (LAK) activity of peritoneal cavity lymphocytes (PCL), compared with treatments with rIL-2 alone or N-CWS alone. After in vitro culture of peritoneal exudate mononuclear cells with rIL-2, the nonadherent population derived from N-CWS-injected tumor-bearing mice showed a significantly higher LAK activity than did that population derived from saline solution-injected mice. When N-CWS-induced PCL were cocultured with either N-CWS-induced macrophages or control macrophages in the presence of rIL-2, their LAK activity was higher than that of control PCL. Therefore, it was suggested that N-CWS-induced PCL themselves have a more potent ability as precursors of LAK cells. Phenotypic analysis on PCL populations revealed that N-CWS-induced PCL contained increased proportions of CD3+CD4-CD8- cells and asialo GM-1+ cells compared with control PCL. These results suggest that N-CWS selectively accumulates potent LAK precursors, namely, CD3+CD4-CD8- T-cells and asialo GM-1+ natural killer cells, at the injection site and that LAK cells are efficiently induced by subsequent administration of rIL-2.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Bacterial Toxins / pharmacology*
  • CD3 Complex
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Cytoskeleton / immunology*
  • Cytotoxicity, Immunologic / drug effects
  • Disease Models, Animal
  • Immunophenotyping
  • Immunotherapy*
  • Interleukin-2 / pharmacology*
  • Killer Cells, Lymphokine-Activated / drug effects*
  • Killer Cells, Lymphokine-Activated / immunology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Lymphocyte Activation / drug effects*
  • Male
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Nocardia*
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Bacterial Toxins
  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Recombinant Proteins