Postsurgical adjuvant chemoimmunotherapy with recombinant interleukin-2 and 1,3-bis-(2-chloroethyl)-1-nitrosurea on spontaneous metastases of a non-immunogenic murine tumour

Giulia Acerbis, Loredana Cleris, Monica Rodolfo, Giorgio Parmiani, Franca Formelli

Research output: Contribution to journalArticlepeer-review

Abstract

The efficacy of the association of recombinant interleukin-2 (rIL-2) with chemotherapy has been investigated on an experimental model representative of clinical tumours, i.e. on post-surgical spontaneous metastases of a non-immunogenic tumour. We used the M5076 ovarian reticulum cell sarcoma, which metastatizes to the liver after intra-footpad implantation. Such a tumour appeared to be non-immunogenic by a variety of commonly used in vivo assays. Four clinically widely employed drugs, i.e. doxorubicin, cis-diamminedichloroplatinum II, cyclophosphamide and 1,3-bis-(2-chloroethyl)-1-nitrosurea (BCNU), were tested and BCNU proved to be the most effective one when administered as single injection at the maximum tolerated dose (33 mg/kg i.p.) 1 day after tumour excision. When moderate doses of rIL-2 (6 × 105 IU in three injections per day for 5 days) were administered at three different intervals after BCNU, namely before the nadir of white blood cells (1 day after BCNU), at the nadir (3 days after BCNU) or at recovery (6 days after BCNU), no increase in BCNU antitumour activity was observed. The same results were obtained by administering rIL-2 for 5 days before BCNU. Higher doses of rIL-2 (1.2 × 106 IU in three injections per day for 5 days), which were always well tolerated in sham-excised non-tumour-bearing mice, proved lethal in two out of four experiments in tumour-bearing animals. In the two experiments in which no lethality was observed, the administration of high doses of rIL-2 1 or 6 days after BCNU significantly increased the antitumour activity of BCNU alone. rIL-2 alone was not active even when administered at high doses. These results indicate that high but not moderate doses of rIL-2 may increase the activity of BCNU against a non-immunogenic tumour. Moreover, they suggest that rIL-2 tolerability is reduced in tumour-bearing mice.

Original languageEnglish
Pages (from-to)383-388
Number of pages6
JournalCancer Immunology, Immunotherapy
Volume34
Issue number6
DOIs
Publication statusPublished - Nov 1992

Keywords

  • Chemoimmunotherapy
  • Murine tumour
  • Non-immunogenic tumour
  • Recombinant interleukin-2

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

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