GM-CSF-secreting vaccines for solid tumors.
Whole tumor cells that secrete GM-CSF have been tested in clinical trials and have demonstrated early evidence of safety and clinical activity. The intradermal administration of these cells induces a massive infiltration of dendritic cells, which process and present tumor antigens to activate tumor-specific CD4+ and CD8+ T-cells. However, trial design flaws limit the phase III evaluation of this vaccine platform. Preclinical and clinical data suggest the development of GM-CSF-secreting tumor vaccines should be continued in combination with drugs that enhance vaccine activity by mitigating immune tolerance or augmenting costimulatory pathways of T-cell activation.
Emens
Leisha A
LA
The Johns Hopkins University and Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, 1650 Orleans Street, Room 409, Bunting Blaustein Cancer Research Building, Baltimore, MD 21231-1000, USA. emensle@jhmi.edu
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D002986:Clinical Trials as Topic / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor