Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells

Maria Vera Ugalde, Nerea Razquin, Jesús Prieto, Ignacio Melero, Puri Fortes, Gloria González-Aseguinolaza

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cancer immunotherapy has been extensively attempted by gene transfer of cytokines with viral vectors. In this work, we compared the therapeutic effects of interleukin 12 and 15 (IL-12 and IL-15) genes transferred to tumor cells or to dendritic cells (DCs), which were subsequently injected into established tumors. For this purpose, we used viral vectors based on simian virus 40 (rSV40). Importantly, we observed that nonmatured DCs infected with rSV40 vectors remained phenotypically immature. Infection of CT-26 tumor cells with rSV40 expressing IL-12 (rSVIL-12) or IL-15 (rSVIL-15) failed to inhibit tumor development. In contrast, the intratumoral administration of syngeneic DCs transduced with rSVIL-12 or rSVIL-15 was associated with a strong antitumor response; up to 40% tumor remissions were achieved with DCs transduced by rSVIL-12 and 73% with DCs expressing IL-15. This antitumor effect correlated with the in vivo priming of tumor-specific CD8+ T lymphocytes. Depletion studies showed that rSVIL-15-mediated antitumor efficacy was mediated mainly by CD8+ T lymphocytes and NK cells. We conclude that (i) SV40-derived vectors are an advantageous alternative to transduce genes into DCs and (ii) DCs transferred with IL-15 have an enhanced capability to induce curative antitumor immunity when injected into malignant lesions.

Original languageEnglish (US)
Pages (from-to)950-959
Number of pages10
JournalMolecular Therapy
Volume12
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Interleukin-15
Natural Killer Cells
Dendritic Cells
Immunity
Interleukin-12
T-Lymphocytes
Injections
Neoplasms
Genes
Simian virus 40
Therapeutic Uses
Immunotherapy
Cytokines
Infection

Keywords

  • Colon carcinoma CT26 cells
  • Dendritic cells
  • Gene therapy
  • IL-12
  • IL-15
  • SV40

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells. / Vera Ugalde, Maria; Razquin, Nerea; Prieto, Jesús; Melero, Ignacio; Fortes, Puri; González-Aseguinolaza, Gloria.

In: Molecular Therapy, Vol. 12, No. 5, 11.2005, p. 950-959.

Research output: Contribution to journalArticle

Vera Ugalde, Maria ; Razquin, Nerea ; Prieto, Jesús ; Melero, Ignacio ; Fortes, Puri ; González-Aseguinolaza, Gloria. / Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells. In: Molecular Therapy. 2005 ; Vol. 12, No. 5. pp. 950-959.
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