title: Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease.
abstract: OBJECTIVE
  Much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of renal cancer. We recently proposed a cyclophosphamide-using nonmyeloablative cell therapy in which donor lymphocyte infusion (DLI) was carried out after the tolerance induction to donor cells. In considering the clinical application of the cyclophosphamide-using cell therapy, attempts to reduce graft-versus-host disease (GVHD) are crucial. 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 renal cancer.
  
  
  METHODS
  We assessed whether a delay in performing DLI from day 1 to day 5 after the cyclophosphamide treatment could reduce the risk of GVHD while preserving antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma, in the cyclophosphamide-using cell therapy.
  
  
  RESULTS
  Regarding the in vivo antitumor effect, there was no difference between DLI on day 1 and day 5 after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with DLI on day 5 decreased the risk of GVHD. In addition, the acquired immunity against RENCA was also observed in the RENCA-rejected mice that had been treated with DLI on day 5.
  
  
  CONCLUSIONS
  Our results show that a delay in DLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate graft-versus-tumor effects from GVHD by reducing the risk of GVHD.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. etom@uro.med.kyushu-u.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Harano
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
authors.forename: Yoriyuki
authors.initials: Y
authors.lastname: Kamiryo
authors.forename: Keijiro
authors.initials: K
authors.lastname: Kiyoshima
authors.forename: Masumitsu
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017690:Cell Transplantation / Q000379:methods; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide