RRC ID 75751
Author Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC.
Title Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.
Journal Proc Natl Acad Sci U S A
Abstract To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4+ and CD8+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, 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. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.
Volume 90(8)
Pages 3539-43
Published 1993-4-15
DOI 10.1073/pnas.90.8.3539
PMID 8097319
PMC PMC46336
MeSH Animals Antibodies, Monoclonal / immunology CD4 Antigens / immunology CD8 Antigens / immunology Carcinoma, Renal Cell / immunology* Carcinoma, Renal Cell / prevention & control Cell Adhesion Molecules / genetics Colonic Neoplasms / immunology* Colonic Neoplasms / prevention & control Female Fibrosarcoma / immunology* Fibrosarcoma / prevention & control Genetic Vectors Granulocyte-Macrophage Colony-Stimulating Factor / genetics Granulocyte-Macrophage Colony-Stimulating Factor / metabolism* Immunization* Intercellular Adhesion Molecule-1 Kidney Neoplasms / immunology* Kidney Neoplasms / prevention & control Lung Neoplasms / immunology* Lung Neoplasms / prevention & control Lymphocyte Depletion Melanoma, Experimental / immunology* Melanoma, Experimental / prevention & control Mice Mice, Inbred BALB C Mice, Inbred C57BL Retroviridae / genetics T-Lymphocyte Subsets / immunology Transfection* Tumor Cells, Cultured / radiation effects
IF 9.412
DNA material pMFGmGM-CSF (RDB01438) pMFGmIL1RA (RDB01440) pMFGmIL2 (RDB01441) pMFGmIL4 (RDB01443) pMFGmIL6 (RDB01444) pMFGhTNF alpha (RDB01450) pMFGmIFN gamma (RDB01454)