Recombinant IL-7/HGFβ hybrid cytokine separates acute graft-versus-host-disease from graft-versus-tumour activity by altering donor T cell trafficking

Abstract

Given that donor T cells from a transplant contribute both the desired graft-versus-tumour (GVT) effect and detrimental graft-versus-host disease (GVHD), strategies to separate GVHD and GVT activity are a major clinical goal. We have previously demonstrated that in vivo administration of a recombinant (r)IL-7/HGFβ hybrid cytokine, consisting of interleukin-7 (IL-7, IL7) and the β-chain of hepatocyte growth factor (HGFβ), significantly inhibits the growth of cancer cells in murine tumour models. The antit-umour effect of rIL-7/HGFβ is related to a marked infiltration T cells in the tumour tissues. We have also shown that GVHD was not induced in rIL-7/HGFβ-treated T cell-depleted allogeneic haematopoietic stem cell transplantation (HSCT) recipients. We show here that, in T cell-replete allogeneic HSCT murine models, rIL-7/HGFβ attenuated acute GVHD (aGVHD), while promoting GVT activity. This was related to an alteration of donor T cell trafficking, with an increased infiltration of donor T cells into tumour tissues and the lympho-haematopoietic system but decreased number of the T cells in the GVHD target organs. Therefore, rIL-7/HGFβ may offer a new tool to alleviate aGVHD while prompting GVT, and to study the molecular regulation of T cell trafficking.