title: 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.
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.|Guizhou Medical University, Guizhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Rood
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA. laijun.lai@uconn.edu.|University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, USA. laijun.lai@uconn.edu.
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D020350:Graft vs Tumor Effect / Q000187:drug effects* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014019:Tissue Donors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D018925:Chemokines; D016207:Cytokines; D015851:Interleukin-7; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor
keywords: T cell trafficking; adhesion molecules; chemokines; graft-versus-host disease; graft-versus-tumour