Autologous neuroblastoma (NB) tumor cells modified to secrete interleukin (IL)-2 (auto–IL-2) can be safely given to patients with advanced neuroblastoma and generate antitumor immune responses. As the benefits of tumor immunization may be greater in patients with minimal residual disease and thus rely on surrogate markers such as immune responses to measure effect, we studied the frequency of immune changes associated with vaccination. Thirteen patients (8 in first remission and 5 after treatment for recurrent NB) received 5 to 8 subcutaneous injections of auto–IL-2 at 0.3×108 cells/kg. The vaccine was well tolerated. Injection site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and dendritic cells. Enzyme-linked immunosorbent spot assays for interferon-γ and IL-5 demonstrated that vaccination produced a rise in circulating CD4+ and CD8+ T cells responsive to stimulation by autologous tumor cells. Median event-free survival was 22 months for patients in first remission and 3 months for all others. Four patients treated in first remission remain alive and 3 without disease recurrence
Russell, H., Strother, D., Mei, Z., Rill, D., Popek, E., Biagi, E., et al. (2008). A Phase 1/2 Study of Autologous Neuroblastoma Tumor Cells Genetically Modified to Secrete IL-2 in Patients With High-risk Neuroblastoma. JOURNAL OF IMMUNOTHERAPY, 31(9), 812-819 [10.1097/CJI.0b013e3181869893].
A Phase 1/2 Study of Autologous Neuroblastoma Tumor Cells Genetically Modified to Secrete IL-2 in Patients With High-risk Neuroblastoma
BIAGI, ETTORE;
2008
Abstract
Autologous neuroblastoma (NB) tumor cells modified to secrete interleukin (IL)-2 (auto–IL-2) can be safely given to patients with advanced neuroblastoma and generate antitumor immune responses. As the benefits of tumor immunization may be greater in patients with minimal residual disease and thus rely on surrogate markers such as immune responses to measure effect, we studied the frequency of immune changes associated with vaccination. Thirteen patients (8 in first remission and 5 after treatment for recurrent NB) received 5 to 8 subcutaneous injections of auto–IL-2 at 0.3×108 cells/kg. The vaccine was well tolerated. Injection site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and dendritic cells. Enzyme-linked immunosorbent spot assays for interferon-γ and IL-5 demonstrated that vaccination produced a rise in circulating CD4+ and CD8+ T cells responsive to stimulation by autologous tumor cells. Median event-free survival was 22 months for patients in first remission and 3 months for all others. Four patients treated in first remission remain alive and 3 without disease recurrenceI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.