GM-CSF-secreting vaccines for solid tumors: moving forward.
Cancer vaccines consisting of intact tumor cells genetically modified to secrete the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) have undergone extensive preclinical development. These vaccines induce the massive accumulation of dendritic cells at the intradermal injection site, which engulf, process, and present tumor antigens to activate tumor-specific T cells. Early phase clinical testing demonstrated promising evidence of safety and bioactivity, although initial phase III clinical trials were unsuccessful. Together, the preclinical and clinical data argue for the continued clinical development of these vaccines, integrating them with standard and novel cancer therapeutics that enhance vaccine activity by overcoming immune tolerance and suppression, and/or augmenting co-stimulatory pathways of T cell activation.
Gupta
Richa
R
Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, Maryland 21231, USA.
Emens
Leisha A
LA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor