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

Summary 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/ HGF β hybrid cytokine, consisting of interleukin‐7 ( IL ‐7, IL 7) and the β‐chain of hepatocyte growth factor ( HGF β), significantly inhibits the growth of cancer cells in murine tumour models. The antit‐umour effect of rIL ‐7/ HGF β is related to a marked infiltration T cells in the tumour tissues. We have also shown that GVHD was not induced in rIL ‐7/ HGF β‐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/ HGF β 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/ HGF β may offer a new tool to alleviate aGVHD while prompting GVT , and to study the molecular regulation of T cell trafficking.