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Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3011-3019
PLENARY PAPER
Sustaining the graft-versus-tumor effect through posttransplant
immunization with granulocyte-macrophage colony-stimulating
factor (GM-CSF)-producing tumor vaccines
Ivan Borrello,
Eduardo M. Sotomayor,
Frédérique-Marie Rattis,
Sara K. Cooke,
Lingping Gu, and
Hyam I. Levitsky
From the Department of Oncology, Johns Hopkins University School of
Medicine, Baltimore, MD.
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.
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