Immunization by Particle-Mediated Transfer of the Granulocyte-Macrophage Colony-Stimulating Factor Gene into Autologous Tumor Cells in Melanoma or Sarcoma Patients: Report of a Phase I/IB Study

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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Immunogenetic Therapy of Human Melanoma Utilizing Autologous Tumor Cells Transduced to Secrete Granulocyte-Macrophage Colony-Stimulating Factor

Human Gene Therapy ◽

10.1089/10430340050015455 ◽

2000 ◽

Vol 11 (6) ◽

pp. 839-850 ◽

Cited By ~ 58

Author(s):

Alfred E. Chang ◽

Qiao Li ◽

D. Keith Bishop ◽

Daniel P. Normolle ◽

Bruce D. Redman ◽

...

Keyword(s):

Tumor Cells ◽

Human Melanoma ◽

Autologous Tumor ◽

Colony Stimulating Factor ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

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Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)–producing tumor vaccines

Blood ◽

10.1182/blood.v95.10.3011 ◽

2000 ◽

Vol 95 (10) ◽

pp. 3011-3019 ◽

Cited By ~ 135

Author(s):

Ivan Borrello ◽

Eduardo M. Sotomayor ◽

Frédérique-Marie Rattis ◽

Sara K. Cooke ◽

Lingping Gu ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Tumor Cells ◽

Immune Reconstitution ◽

Autologous Tumor ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract 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.

Download Full-text