Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma

Raphaël F. Rousseau, Ann E. Haight, Charlotte Hirschmann-Jax, Eric S. Yvon, Donna R. Rill, Zhuyong Mei, Susan C. Smith, Shannon Inman, Kristine Cooper, Pat Alcoser, Bambi Grilley, Adrian Gee, Edwina Popek, Andrew Davidoff, Laura C. Bowman, Malcolm K. Brenner, Douglas Strother

Research output: Contribution to journalArticle

102 Scopus citations

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. The safety and immunologic effects of this approach in humans were tested in 21 patients with relapsed or refractory neuroblastoma. They received up to 8 subcutaneous injections of a vaccine combining lymphotactin (Lptn)- and interleukin-2 (IL-2)-secreting allogeneic neuroblastoma cells in a dose-escalating scheme. Severe adverse reactions were limited to reversible panniculitis in 5 patients and bone pain in 1 patient. Injection-site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and Langerhans cells. Systemically, the vaccine produced a 2-fold (P = .035) expansion of CD4+ T cells, a 3.5-fold (P = .039) expansion of natural killer (NK) cells, a 2.1-fold (P = .014) expansion of eosinophils, and a 1.6-fold (P = .049) increase in serum IL-5. When restimulated in vitro by the immunizing cell line, T cells collected after vaccination showed a 2.3-fold increase (P = .02) of T-helper (TH2)-type CD3+IL-4+ cells. Supernatant collected from restimulated cells showed increased amounts of IL-4 (11.4-fold; P = .021) and IL-5 (8.7-fold; P = .002). Six patients had significant increases in NK cytolytic activity. Fifteen patients made immunoglobulin G (IgG) antibodies that bound to the immunizing cell line. Measurable tumor responses included complete remission in 2 patients and partial response in 1 patient. Hence, allogeneic tumor cell vaccines combining transgenic Lptn with IL-2 appear to have little toxicity in humans and can induce an antitumor immune response.

Original languageEnglish (US)
Pages (from-to)1718-1726
Number of pages9
JournalBlood
Volume101
Issue number5
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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