Efficacy of repeated cycles of chemo-immunotherapy with thymosin α1 and interleukin-2 after intraperitoneal 5-fluorouracil delivery

Gianfranco Silecchia, Enrico Guarino, Paola Sinibaldi-Vallebona, Pasquale Pierimarchi, Angelo Restuccia, Erasmo Spaziani, Paola Bernard, Cynthia Tuthill, Enrico Garaci, Guido Rasi

Research output: Contribution to journalArticlepeer-review

Abstract

We have used chemo-immunotherapy with 5-fluorouracil (5-FU), thymosin α1 (Tα1) and interleukin-2 (IL-2) to treat multiple liver metastases from colorectal cancer induced by DHD/K12 cells in syngeneic BDIX rats, comparing one and two cycles of treatment, and different treatment combinations. 5-FU was delivered loco-regionally as a continuous infusion via an intraperitoneal (i.p.) catheter from a subcutaneously implanted mini-pump, a method we developed for this study. We show here that two cycles of a triple chemoimmunotherapy regimen significantly increased the average survival time compared to one cycle, and compared to untreated controls or those treated with two cycles of 5-FU alone. At 150 days, two rats treated with two cycles of triple therapy were cured, showing no signs of cancer at autopsy; all the other rats died before this time. Triple chemo-immunotherapy resulted in significantly fewer extra-hepatic metastases than in the controls and in those treated with 5-FU only. Further, we found that two cycles of triple treatment significantly increased the absolute number of peripheral T cells expressing IL-2 receptor, CD4 and CD8 compared to controls. We conclude that two cycles of chemo-immunotherapy with 5-FU, Tα1 and IL-2 were superior to one cycle of treatment and to other treatments tested. Our results suggest that the triple therapy acts by increasing numbers of effector T cells. This method shows promise for the use of multi-cycle chemo-immunotherapy in the treatment of unresectable metastases of colorectal cancer in humans.

Original languageEnglish
Pages (from-to)172-178
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume48
Issue number4
DOIs
Publication statusPublished - 1999

Keywords

  • 5-FU
  • Interleukin-2 Survival
  • T cells
  • Thymosin α1

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

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