TY - JOUR
T1 - Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation
AU - Takeuchi, Ario
AU - Eto, Masatoshi
AU - Tatsugami, Katsunori
AU - Yamada, Hisakata
AU - Yokomizo, Akira
AU - Shiota, Masaki
AU - Itsumi, Momoe
AU - Inokuchi, Junichi
AU - Kiyoshima, Keijiro
AU - Dejima, Takashi
AU - Imada, Kenjiro
AU - Naito, Seiji
AU - Yoshikai, Yasunobu
N1 - Funding Information:
The authors gratefully acknowledge the funding supports from Kakenhi , Grant No. 26861274 and from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.
Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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. •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).•RLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate GVT effects from GVHD by reducing the risk of GVHD.•In addition, we showed that serum IFN-γ levels were significantly elevated in animals received RLI and that the origin of producing IFN-γ was host-derived CD4 and CD8 T cells in this model.
AB - 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. •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).•RLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate GVT effects from GVHD by reducing the risk of GVHD.•In addition, we showed that serum IFN-γ levels were significantly elevated in animals received RLI and that the origin of producing IFN-γ was host-derived CD4 and CD8 T cells in this model.
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U2 - 10.1016/j.trim.2014.12.001
DO - 10.1016/j.trim.2014.12.001
M3 - Article
C2 - 25527449
AN - SCOPUS:84926284038
SN - 0966-3274
VL - 32
SP - 131
EP - 139
JO - Transplant Immunology
JF - Transplant Immunology
IS - 2
ER -
