1. ¹Molecular Immunology Laboratory, Transgene SA, Strasbourg 67082, France
2. ²Animal Facilities, Transgene SA, Strasbourg 67082, France
3. ³Adenovirology Laboratory, Transgene SA, Strasbourg 67082, France
4. ⁴Immunohistochemistry Laboratory, Transgene SA, Strasbourg 67082, France
5. ⁵Division of Medical and Regulatory Affairs, Transgene SA, Strasbourg 67082, France

Correspondence: Dr Bastien Calmels, Molecular Immunology Laboratory, Transgene SA, Strasbourg 67082, France. E-mail: calmels@transgene.fr

Received 14 June 2004; Published online 8 October 2004.

Abstract

Recent evidence has resurrected the concept of specialized populations of T lymphocytes that are able to suppress an antigen-specific immune response. T-regulatory cells (T-reg) have been characterized as CD4+ CD25+ T cells. Previous reports describing differential gene expression analysis have shown that the glucocorticoid-induced tumor necrosis family receptor family-related gene (GITR) is upregulated in these cells. Furthermore, antibodies specific for GITR have been shown to inhibit the T-suppressor function of CD4+ CD25+ T-reg. The ligands for both mouse and human GITR have been cloned recently. We have inserted the sequences for natural, membrane-bound GITR-ligand (GITR-L) and a truncated secreted form of GITR-L (GITR-Lsol) into the adenovirus-5 genome. Coculture experiments show that cells infected with Ad-GITR-L and supernatants from cells infected with Ad-GITR-Lsol can increase the proliferation of both CD4+ CD25- and CD8+ T cells in response to anti-CD3 stimulation, in the presence, as well as in the absence, of CD4+ CD25+ T cells. The virus constructs were injected into growing B16 melanoma tumors. Ad-GITR-L was shown to attract infiltration with both CD4+ and CD8+ T cells. Both constructs were shown to inhibit tumor growth.