title: Renal cancer treatment with low levels of mixed chimerism induced by nonmyeloablative regimen using cyclophosphamide in mice.
abstract: Recently, much attention has been paid to nonmyeloablative allogeneic stem cell transplantation 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 activity associated with this treatment. Hence, the segregation of the graft-versus-tumor 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. Here, we show a modified cyclophosphamide-induced tolerance system for the treatment of murine renal cell carcinoma, RENCA, by shifting the equal balance between graft-versus-host and host-versus-graft reactions toward graft-versus-host reaction with donor lymphocyte infusion. Our results clearly show the antitumor activity against RENCA with only low levels of mixed chimerism in the periphery and the in vivo and in vitro acquired immunity against RENCA even when mixed chimerism is almost undetectable. Because the withdrawal of mixed chimerism reduces the risk of GVHD, the antitumor activity is thus sequentially segregated from the initial GVHD in our model. We believe that this is the first unique model system of nonmyeloablative allogeneic hemopoietic cell transplantation to ever be reported for the treatment of renal cancer.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Harano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.forename: Toshiro
authors.initials: T
authors.lastname: Iwai
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.forename: Keijiro
authors.initials: K
authors.lastname: Kiyoshima
authors.forename: Yoriyuki
authors.initials: Y
authors.lastname: Kamiryo
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; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018183:Transplantation Chimera / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide