Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity

Bernd Gansbacher, Karen Zier, Brian Daniels, Kathy Cronin, Rajat Bannerji, Eli Gilboa

Research output: Contribution to journalArticle

653 Scopus citations

Abstract

To study the effects of localized secretion of cytokines on tumor progression, the gene for human interleukin 2 (IL-2) was introduced via retroviral vectors into CMS-5 cells, a weakly immunogenic mouse fibrosarcoma cell line of BALB/c origin. Secretion of low levels of IL-2 from the tumor cells abrogated their tumorigenicity and induced a long-lasting protective immune response against a challenge with a tumorigenic dose of parental CMS-5 cells. Co-injection of IL-2-producing CMS-5 cells with unmodified tumor cells inhibited tumor formation even when highly tumorigenic doses of CMS-5 cells were used. Cytolytic activity in mice injected with parental CMS-5 cells was transient and was greatly diminished 3 wk after injection, as commonly observed in tumor-bearing animals. However, in mice injected with IL-2-producing cells, tumor-specific cytolytic activity persisted at high levels for the duration of the observation period (at least 75 d). High levels of tumor-specific cytolytic activity could also be detected in parental CMS-5 tumor-bearing animals 18 d after inoculation with tumor cells, if IL-2-producing CMS-5 cells but not unmodified parental tumor cells were used as targets. These studies highlight the potential advantages of localized secretion of cytokines mediated via gene transfer to induce potent anti-tumor immune responses.

Original languageEnglish (US)
Pages (from-to)1217-1224
Number of pages8
JournalJournal of Experimental Medicine
Volume172
Issue number4
DOIs
StatePublished - Oct 1 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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