A phase 1/2 study of autologous neuroblastoma tumor cells genetically modified to secrete il-2 in patients with high-risk neuroblastoma

Heidi V. Russell, Douglas Strother, Zhuyong Mei, Donna Rill, Edwina Popek, Ettore Biagi, Eric Yvon, Malcolm Brenner, Raphael Rousseau

Research output: Contribution to journalArticle

31 Scopus citations

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 x 10 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-gamma 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.

Original languageEnglish (US)
Pages (from-to)812-819
Number of pages8
JournalJournal of immunotherapy (Hagerstown, Md. : 1997)
Volume31
Issue number9
DOIs
StatePublished - 2008

Keywords

  • Gene therapy
  • Neuroblastoma
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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