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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.

cancer science

Combination 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