| Abstract: |
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. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
| Keywords: |
cancer survival; controlled study; treatment outcome; survival analysis; transplantation, homologous; mortality; cancer growth; multimodality cancer therapy; nonhuman; combined modality therapy; animal cell; mouse; animal; animals; mice; animal tissue; cancer immunotherapy; animal experiment; animal model; colonic neoplasms; hematopoietic stem cell transplantation; cell line, tumor; monoclonal antibody; disease model; cancer inhibition; immunology; antibodies, monoclonal; acute graft versus host disease; myeloablative conditioning; tumor cell line; graft versus host reaction; transplantation conditioning; donor lymphocyte infusion; allogeneic hematopoietic stem cell transplantation; cd4 antigen; disease models, animal; graft vs host disease; antigens, cd4; colon adenocarcinoma; adoptive immunotherapy; immunotherapy, adoptive; allotransplantation; mouse model; lymphocyte transfusion; graft-versus-host disease; graft-versus-tumor; procedures; cd4; male; priority journal; article; cd4 antibody
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