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

J Immunother. Feb-Mar 2007;30(2):227-33. doi: 10.1097/01.cji.0000211335.14385.57.

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-gamma 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Child
  • Female
  • Genetic Engineering
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology*
  • Lymphokines / genetics
  • Lymphokines / immunology*
  • Male
  • Neuroblastoma / genetics
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy*
  • Peripheral Nervous System Neoplasms / therapy*
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / immunology*
  • Treatment Outcome
  • Vaccination

Substances

  • Cancer Vaccines
  • Interleukin-2
  • Lymphokines
  • Sialoglycoproteins
  • lymphotactin