Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma
Robert J. Soiffer,Thomas R. Lynch,Martin C. Mihm,Kenneth Jung,Catherine Rhuda,Jan C. Schmollinger,F S Hodi,L Liebster,P Lam,Steven J. Mentzer,Samuel Singer,Kenneth K. Tanabe,Cosimi Ab,Rosemary B. Duda,Arthur J. Sober,Atul K. Bhan,John F. Daley,Donna Neuberg,Gareth Parry,J Rokovich,L Richards,J Drayer,Anton Berns,Shirley M. Clift,Lawrence K. Cohen,Richard C. Mulligan,Glenn Dranoff +26 more
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It is demonstrated that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.Abstract:
We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte–macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.read more
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Current protocols in immunology
TL;DR: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, and animal models of autoimmune and inflammatory diseases.
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Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity
Glenn Dranoff,Elizabeth M. Jaffee,Audrey J. Lazenby,Paul Golumbek,Hyam I. Levitsky,Katja Brose,Valerie Jackson,Hirofumi Hamada,Drew M. Pardoll,Richard C. Mulligan +9 more
TL;DR: The results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines and the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone.
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