Phase I trial of vaccination with autologous neuroblastoma tumor cells genetically modified to secrete IL-2 and lymphotactin

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

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)227-233
Number of pages7
JournalJournal of Immunotherapy
Issue number2
StatePublished - Feb 2007


  • Gene-therapy
  • Neuroblastoma
  • Phase I
  • Vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology


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