Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease

Masatoshi Eto, Masahiko Harano, Katsunori Tatsugami, Mamoru Harada, Yoriyuki Kamiryo, Keijiro Kiyoshima, Masumitsu Hamaguchi, Masazumi Tsuneyoshi, Yasunobu Yoshikai, Seiji Naito

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish
Pages (from-to)1029-1035
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number3
DOIs
Publication statusPublished - Feb 1 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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