title: Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation.
abstract: BACKGROUND
  Nonmyeloablative allogeneic stem cell transplantation (SCT) is an option for the treatment of metastatic renal cancer. Mature donor T cells cause graft versus-host disease (GVHD) although they are also the main mediators of the beneficial graft-versus-tumor (GVT) activity associated with this treatment. Hence, the segregation of GVT activity from GVHD is an important challenge in managing the clinical course of treatment. We previously reported a series of studies regarding the allograft tolerance induced by allogeneic spleen cells (with bone marrow cells) and cyclophosphamide in mice.
  
  
  METHODS
  The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma with recipient lymphocyte infusion (RLI).
  
  
  RESULTS
  Regarding the in vivo antitumor effect, there was a significant difference between RLI and no lymphocyte infusion after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with RLI decreased the risk of GVHD as compared with donor lymphocyte infusion. In addition, the acquired immunity against RENCA was clearly observed in RLI-treated mice.
  
  
  CONCLUSIONS
  Our results show that RLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate GVT effects from GVHD by reducing the risk of GVHD. We considered that this was the first report to provide the evidence of nonmyeloablative allogeneic SCT with RLI for the treatment of renal cell carcinoma which never induce complete chimerism.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ario
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: etom@kumamoto-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.affiliation: Division of Host Defense, Research Center for Prevention of Infectious Disease, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Momoe
authors.initials: M
authors.lastname: Itsumi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Inokuchi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Kiyoshima
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Dejima
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Imada
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.affiliation: Division of Host Defense, Research Center for Prevention of Infectious Disease, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D064591:Allografts; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis; D033581:Stem Cell Transplantation
keywords: Cyclophosphamide; Recipient lymphocyte infusion; Renal cancer