Open AccessCombination of anti‐ CD 4 antibody treatment and donor lymphocyte infusion ameliorates graft‐ versus ‐host disease while preserving graft‐ versus ‐tumor effects in murine allogeneic hematopoietic stem cell transplantation
Author(s) -
Ueha Satoshi,
Yokochi Shoji,
Ishiwata Yoshiro,
KosugiKanaya Mizuha,
Shono Yusuke,
Shibayama Shiro,
Ito Satoru,
Matsushima Kouji
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13346
Subject(s) - donor lymphocyte infusion , medicine , graft versus host disease , hematopoietic stem cell transplantation , immunotherapy , immunology , transplantation , lymphocyte , refractory (planetary science) , stem cell , disease , haematopoiesis , cancer research , immune system , biology , genetics , astrobiology
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 ). CD 4 + T cells have been implicated in several aspects of GVHD , and suppress antitumor CD 8 + 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‐ CD 4 mA b substantially ameliorated GVHD while preserving antitumor effects, leading to improved survival in myeloablative allo‐ HSCT . Late treatment with anti‐ CD 4 mA b also ameliorated GVHD to some extent. Donor lymphocyte infusion in GVHD mice treated with anti‐ CD 4 mA b further suppressed tumor growth without exacerbating GVHD . Collectively, our results suggest that myeloablative allo‐ HSCT followed by anti‐ CD 4 mA b treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.