¹Unité INSERM 524, IRCL, Lille, France

²Laboratoire de recherche sur les maladies inflammatoires chroniques de l'intestin, CHU Lille (CRI 4U004B), Lille, France

³Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France

⁴Service des Maladies du Sang, CHU Lille, Lille, France

Correspondence to: B Quesnel, Service des Maladies du Sang, CHU Lille, Rue Polonovski, 59037 Lille, France; Fax: (33) 3 20 44 40 94

IL12 is an essential cytokine for the generation of T helper 1 response, natural killer (NK) cells and cytotoxic T lymphocyte (CTL) stimulation. CD154 triggers CD40 on antigen-presenting cells, thus inducing antigen presentation to the immune system and production of IL12. As IL12 and CD154 share several pathways mediating immune response, we investigated in an aggressive murine model of acute leukemia the relative antileukemic efficiency of IL12, CD154 and IL12 + CD154 gene transfer. Live leukemic cells transduced by IL12, CD154, and IL12 + CD154 showed reduced leukemogenicity but CD154 protective effect was reduced when 10⁶ leukemic cells were injected. Vaccines with lethally irradiated IL12-transduced cells were able to cure mice previously injected with 10⁴ leukemic cells and adoptive transfer of IL12-induced antileukemic immunity protected recipient mice. NK cytotoxicity was enhanced in mice vaccinated with leukemic cells transduced by IL12, CD154, and CD154 + IL12. IL12 transduced cells induced IFN- mRNA in CD4⁺ and CD8⁺ T cells isolated from the spleen of vaccinated animals, however, in vivo depletion experiments showed that IL12 vaccine effect was CD4⁺ but not CD8⁺ T cell dependent. We conclude that IL12 gene is a more potent candidate than CD154 for gene therapy of acute leukemia.

Leukemia (2002) 16, 1637-1644. doi:10.1038/sj.leu.2402590

IL12; gene therapy; CD154; vaccine; leukemia