In murine models, transgenic chemokine-cytokine tumor vaccines overcome many of the limitations of single-agent immunotherapy by producing the sequence of T-cell attraction followed by proliferation of tumor antigen-activated clones. The safety and immunologic effects of this approach in humans were tested in 7 patients with relapsed or refractory neuroblastoma. They each received up to 8 subcutaneous injections of a vaccine combining lymphotactin—and interleukin-2 (IL-2)—secreting autologous neuroblastoma cells in a dose-escalating scheme. Adverse events were limited to grade 1 or 2 localized reactions in all patients, pain in 3 patients, and fever in 3 patients. Injection site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and dendritic cells with a decrease in dendritic cells from the first to the second vaccination. Systemically, vaccine was associated with increased tumor recognition as measured by enzyme-linked immunosorbent spot assays. Two patients had interferon-γ predominant responses and 3 had IL-5 predominant responses. Only 1 patient received all 8 injections, 1 patient stopped the study early, and all other patients progressed before completion of the study. Hence, autologous tumor cell vaccines combining transgenic lymphotactin with IL-2 seem to have little toxicity in humans and can induce an antitumor immune response. In this setting, the immune response was insufficient to overcome active recurrent neuroblastoma

Russell, H., Strother, D., Mei, Z., Rill, D., Popek, E., Biagi, E., et al. (2007). Phase I Trial of Vaccination With Autologous Neuroblastoma Tumor Cells Genetically Modified to Secrete IL-2 and Lymphotactin. JOURNAL OF IMMUNOTHERAPY, 30(2), 227-233 [10.1097/01.cji.0000211335.14385.57].

Phase I Trial of Vaccination With Autologous Neuroblastoma Tumor Cells Genetically Modified to Secrete IL-2 and Lymphotactin

BIAGI, ETTORE;
2007

Abstract

In murine models, transgenic chemokine-cytokine tumor vaccines overcome many of the limitations of single-agent immunotherapy by producing the sequence of T-cell attraction followed by proliferation of tumor antigen-activated clones. The safety and immunologic effects of this approach in humans were tested in 7 patients with relapsed or refractory neuroblastoma. They each received up to 8 subcutaneous injections of a vaccine combining lymphotactin—and interleukin-2 (IL-2)—secreting autologous neuroblastoma cells in a dose-escalating scheme. Adverse events were limited to grade 1 or 2 localized reactions in all patients, pain in 3 patients, and fever in 3 patients. Injection site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and dendritic cells with a decrease in dendritic cells from the first to the second vaccination. Systemically, vaccine was associated with increased tumor recognition as measured by enzyme-linked immunosorbent spot assays. Two patients had interferon-γ predominant responses and 3 had IL-5 predominant responses. Only 1 patient received all 8 injections, 1 patient stopped the study early, and all other patients progressed before completion of the study. Hence, autologous tumor cell vaccines combining transgenic lymphotactin with IL-2 seem to have little toxicity in humans and can induce an antitumor immune response. In this setting, the immune response was insufficient to overcome active recurrent neuroblastoma
Articolo in rivista - Articolo scientifico
Neuroblastoma; vaccination; gene therapy; IL-2; lymphotactin
English
2007
30
2
227
233
none
Russell, H., Strother, D., Mei, Z., Rill, D., Popek, E., Biagi, E., et al. (2007). Phase I Trial of Vaccination With Autologous Neuroblastoma Tumor Cells Genetically Modified to Secrete IL-2 and Lymphotactin. JOURNAL OF IMMUNOTHERAPY, 30(2), 227-233 [10.1097/01.cji.0000211335.14385.57].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/46173
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