Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients 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 granulocytemacrophage 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 colonystimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

“…Granulocyte-macrophage colony stimulating factor is a powerful chemoattractant of antigen-presenting cells, inducing their maturation into dendritic cells, thereby enhancing T-cell responses. [9][10][11] IL-2 is a cytokine, which stimulates the proliferation of cytotoxic T cells (CTLs), helper T cells and natural killer cells, all of which may contribute to a cellular antitumor immune response. 12 IL-7 is a pleiotropic cytokine inducing CD8 + and CD4 + T-cell proliferation, and particularly the activation of CTLs.…”

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

“…36 Despite these new vector developments the retroviral approach for delivery of cytokine genes to autologous tumor cells is thusfar the most widely used in the clinic, also for delivery of GM-CSF. 1,4,37 In the present study we have studied transgene expression using the recombinant SFV system. The recombinant SFV system has several advantages.…”

“…Possibilities that are already explored in the clinic involve immunization with autologous tumor cells, genetically modified with recombinant viral vectors to produce interferon-gamma, IL-4, IL-12, and GM-CSF. [1][2][3][4][5][6] At present, GM-CSF appears to be the most efficient cytokine for obtaining optimal immune responses. 7 Within the context of the use of cytokine gene-modified autologous tumor cell vaccines, currently, in the clinic retrovirus vectors are applied most widely for delivery of the cytokine gene to the tumor cells, [7][8][9][10][11] although other viral delivery systems are also under investigation.…”

Immunity against breast cancer by TERT DNA vaccine primed with chemokine CCL21

“…As adjuvants, IFN-g and GM-CSF have been shown to enhance tumor antigen-specific effects. 26,33 Enhanced production of IFN-g, GM-CSF and TNF-a are involved in tumor antigen-specific immunity. Prolonged and enhanced secretion of IFN-g by CD4 þ T cells may contribute to maintenance of an effective TERT-specific immune response and break immune tolerance.…”