Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not only a well-established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo-HSCT to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft-versus-host disease (GVHD). CD4+ T cells have been implicated in several aspects of GVHD, and suppress antitumor CD8+ T-cell responses. In the present study, we investigated clinically applicable allo-HSCT protocols designed to maximize antitumor effects while reducing the risk of GVHD. We used a mouse model of allo-HSCT with s.c. tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute GVHD. Early treatment with anti-CD4 mAb substantially ameliorated GVHD while preserving antitumor effects, leading to improved survival in myeloablative allo-HSCT. Late treatment with anti-CD4 mAb also ameliorated GVHD to some extent. Donor lymphocyte infusion in GVHD mice treated with anti-CD4 mAb further suppressed tumor growth without exacerbating GVHD. Collectively, our results suggest that myeloablative allo-HSCT followed by anti-CD4 mAb treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.
Keywords: Allogeneic hematopoietic stem cell transplantation; CD4; donor lymphocyte infusion; graft-versus-host disease; graft-versus-tumor.
© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.