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

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.

• Authors: Heidi V Russell, Douglas Strother, Zhuyong Mei, Donna Rill, Edwina Popek, Ettore Biagi, Eric Yvon, Malcolm Brenner, Raphael Rousseau
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2007 Feb-Mar Vol. 30 Issue 2 Pg. 227-33 ISSN: 1524-9557 [Print] United States
• PMID: 17471169 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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