title: In vivo antitumor activity of a recombinant IL-7/HGFbeta hybrid cytokine in mice.
abstract: The immune cytokine interleukin (IL)-7 and the β-chain of hepatocyte growth factor (HGF) aggregate to form a naturally occurring heterodimer that stimulates the growth of common lymphoid progenitors and immature B and T lymphoid cells. We have cloned and expressed the heterodimer as a single-chain hybrid cytokine [recombinant (r) IL-7/HGFβ], which stimulates short-term hematopoietic stem cells as well as lymphoid precursors. Inasmuch as IL-7 and HGF are known to have antitumor and protumor activities, respectively, we determined here whether either of these activities is exhibited by rIL-7/HGFβ. We show that the in vivo administration of rIL-7/HGFβ markedly inhibits the growth of newly initiated and established tumors and the formation of pulmonary metastases in murine models of colon cancer and melanoma. The antitumor effect of rIL-7/HGFβ correlated with a marked increase in the number of tumor-infiltrating CD4(+) and CD8(+) T cells and activated dendritic cells. A major role for these immune cells in tumor suppression was indicated by the inability of rIL-7/HGFβ to inhibit the growth of tumor cells in vitro and in congenitally athymic mice. Analysis of interferon-γ-secreting T cells showed that the immune response was tumor specific. Our findings justify further evaluation of rIL-7/HGFβ as a novel experimental cancer therapy.
authors.affiliation: Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. llai@neuron.uchc.edu
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
authors.forename: Jingjun
authors.initials: J
authors.lastname: Jin
authors.forename: Irving
authors.initials: I
authors.lastname: Goldschneider
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D015851:Interleukin-7 / Q000737:chemistry / Q000494:pharmacology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D015851:Interleukin-7; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor