TY - JOUR
T1 - Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)- producing tumor vaccines
AU - Borrello, Ivan
AU - Sotomayor, Eduardo M.
AU - Rattis, Frédérique Marie
AU - Cooke, Sara K.
AU - Gu, Lingping
AU - Levitsky, Hyam I.
PY - 2000/5/15
Y1 - 2000/5/15
N2 - For many cancers, autologous bone marrow transplantation (BMT) achieves a minimal residual disease state, yet relapse rates remain high. Using a syngeneic murine bone marrow transplant model, we demonstrate that vaccination with irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing autologous tumor cells is effective in the post-BMT period and actually results in a greater tumor-free survival than vaccination in the nontransplant setting. Employing T cells specific for a model tumor-antigen, we find that transplantation of the tumor-bearing host results in a massive expansion and activation of tumor-specific T cells in the early posttransplant period, but this response rapidly declines in association with tumor progression, immunization with irradiated GM-CSF tumor cells during the period of immune reconstitution results in the sustained amplification and activation of this response that closely correlates with freedom from relapse. These results demonstrate the feasibility of integrating GM-CSF vaccines in the postautologous BMT setting and suggest mechanisms that may contribute to the observed efficacy of immunization during the critical period of immune reconstitution. (C) 2000 by The American Society of Hematology.
AB - For many cancers, autologous bone marrow transplantation (BMT) achieves a minimal residual disease state, yet relapse rates remain high. Using a syngeneic murine bone marrow transplant model, we demonstrate that vaccination with irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing autologous tumor cells is effective in the post-BMT period and actually results in a greater tumor-free survival than vaccination in the nontransplant setting. Employing T cells specific for a model tumor-antigen, we find that transplantation of the tumor-bearing host results in a massive expansion and activation of tumor-specific T cells in the early posttransplant period, but this response rapidly declines in association with tumor progression, immunization with irradiated GM-CSF tumor cells during the period of immune reconstitution results in the sustained amplification and activation of this response that closely correlates with freedom from relapse. These results demonstrate the feasibility of integrating GM-CSF vaccines in the postautologous BMT setting and suggest mechanisms that may contribute to the observed efficacy of immunization during the critical period of immune reconstitution. (C) 2000 by The American Society of Hematology.
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U2 - 10.1182/blood.v95.10.3011
DO - 10.1182/blood.v95.10.3011
M3 - Article
C2 - 10807763
AN - SCOPUS:0034658049
SN - 0006-4971
VL - 95
SP - 3011
EP - 3019
JO - Blood
JF - Blood
IS - 10
ER -