Renal cancer treatment with low levels of mixed chimerism induced by nonmyeloablative regimen using cyclophosphamide in mice

Masahiko Harano, Masatoshi Eto, Toshiro Iwai, Katsunori Tatsugami, Keijiro Kiyoshima, Yoriyuki Kamiryo, Masazumi Tsuneyoshi, Yasunobu Yoshikai, Seiji Naito

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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.

Original languageEnglish
Pages (from-to)10032-10040
Number of pages9
JournalCancer Research
Volume65
Issue number21
DOIs
Publication statusPublished - Nov 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Harano, M., Eto, M., Iwai, T., Tatsugami, K., Kiyoshima, K., Kamiryo, Y., Tsuneyoshi, M., Yoshikai, Y., & Naito, S. (2005). Renal cancer treatment with low levels of mixed chimerism induced by nonmyeloablative regimen using cyclophosphamide in mice. Cancer Research, 65(21), 10032-10040. https://doi.org/10.1158/0008-5472.CAN-05-0457