Amount of interleukin 12 available at the tumor site is critical for tumor regression

Mario P. Colombo, Maddalena Vagliani, Fabio Spreafico, Mariella Parenza, Claudia Chiodoni, Cecilia Melani, Antonella Stoppacciaro

Research output: Contribution to journalArticle

Abstract

The C26 colon carcinoma is resistant to systemic recombinant interleukin 12 (rIL-12) therapy. Transduction of C26 with genes encoding the two subunits of murine IL-12 to release 30-80 pg/ml resulted in delayed tumor onset after injection of 5 x 104 cells into syngeneic BALB/c mice and in 40% tumor regression after injection into CD4-depleted mice. Here, we analyzed the activity of rIL-12 (1 μg/day) against C26 grown into CD4-depleted mice. Like in mice given injections of interleukin 12 (IL-12) gene-transduced C26 cells, depletion of CD4+ cells led to tumor regression in 6 of 14 mice, and immunocytochemical characterization of tumor-infiltrating leukocytes showed abundant infiltration by CD8+ T cells and asialoGM1+ natural killer cells, which were scanty in tumors from nondepleted mice. On the basis of the percentage of tumor regression and leukocyte infiltration we can conclude that, in the C26 system, systemic rIL-12 (1 μg/day) produces the same results as 30-80 pg/ml IL-12 released at the tumor site. A new polycistronic retroviral vector was then used to increase the amount of IL-12 produced by C26-transduced cells. C26 cells releasing 5 ng/ml IL-12, nearly 100 times more than the above-mentioned transduced cells, were tumorigenic in less than 50% of the mice given injections of 5 x 104 cells. In mice given injections of 5 x 105 cells, an initial tumor take of 100% followed by a complete tumor regression. Tumor regression was associated with infiltration of CD8+ and asialoGM1+ cells, and mice that remained tumor free were immune to a rechallenge of nontransduced C26 cells. The results indicate that the amount of IL-12 made available at the tumor site may determine both the type and number of infiltrating leukocytes and the events leading to tumor regression as well as it may overcame host immunosuppression.

Original languageEnglish
Pages (from-to)2531-2534
Number of pages4
JournalCancer Research
Volume56
Issue number11
Publication statusPublished - Jun 1 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Amount of interleukin 12 available at the tumor site is critical for tumor regression'. Together they form a unique fingerprint.

Cite this