Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease.
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.
Eto
Masatoshi
M
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. etom@uro.med.kyushu-u.ac.jp
Harano
Masahiko
M
Tatsugami
Katsunori
K
Harada
Mamoru
M
Kamiryo
Yoriyuki
Y
Kiyoshima
Keijiro
K
Hamaguchi
Masumitsu
M
Tsuneyoshi
Masazumi
M
Yoshikai
Yasunobu
Y
Naito
Seiji
S
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
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide