Marked reduction of subcutaneous tumor growth by intraperitoneal administration of recombinant human interleukin 2 with a cell accumulator, proteose-peptone, in mice

Cancer Res. 1989 Jan 15;49(2):284-8.

Abstract

The growth of 3-methylcholanthrene-induced fibrosarcomas, Meth 1 and Meth A, was strongly suppressed by a combination of recombinant human interleukin 2 (rIL-2) with proteose-peptone (PP) administered i.p. to syngeneic mice. When 1 ml of 10% PP was injected i.p. on Day 6 followed by rIL-2 (50 micrograms) administered i.p. on Days 7 and 8 after the s.c. inoculation of tumor cells into female BALB/c mice, the tumors regressed. A similar result was also obtained when 12.5 micrograms of rIL-2 were injected on Days 7, 8, and 9 after s.c. inoculation of Meth 1 cells. The treatment with an anti-asialo-GM1 antibody had no effect on the regression of the Meth 1 tumor induced by the combination. However, the combined treatment with rIL-2 and PP did not suppress the growth of the Meth 1 tumor in adult thymectomized, irradiated, and fetal liver cell-reconstituted BALB/c mice. Therefore, this suggests that the T-cells might be the principal effectors of this antitumor system. The cytolytic activity of splenocytes and peritoneal exudate cells from Meth 1 tumor-bearing mice against Meth 1 cells was significantly augmented by the combined treatment. This peritoneal exudate cell also showed cytolytic activity against other target cells such as Meth A, antigenically distinct from Meth 1, YAC-1, a leukemic cell line sensitive to natural killer cells, and EL-4, a lymphoma cell line resistant to natural killer cells. The cytolytic activity of these effectors was reduced by the treatment with anti-thy1.2 antibody plus complement. The adherent cells in this peritoneal cavity had only a small cytolytic activity on Meth 1 and Meth A targets. The mechanism of antitumor immunity by rIL-2 in combination with PP and the therapeutic availability of this lymphokine are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caseins / pharmacology*
  • Cytotoxicity, Immunologic / drug effects
  • Fibrosarcoma / drug therapy*
  • Fibrosarcoma / pathology
  • Interleukin-2 / therapeutic use*
  • Methylcholanthrene
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / pharmacology*
  • Recombinant Proteins / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology

Substances

  • Caseins
  • Interleukin-2
  • Peptide Fragments
  • Recombinant Proteins
  • proteose-peptone
  • Methylcholanthrene