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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-08-2493. This Article Full Text (PDF) All Versions of this Article: 2002-08-2493v1 101/5/1718    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rousseau, R. F Articles by Strother, D. Search for Related Content PubMed PubMed Citation Articles by Rousseau, R. F Articles by Strother, D. Social Bookmarking                   What's this? Submitted August 14, 2002 Accepted September 24, 2002 Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma Raphael 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, and Douglas Strother Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA Department of Pathology, Baylor College of Medicine, Houston, TX, USA Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN, USA * Corresponding author; email: rfrousse{at}txccc.org. 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 was tested in 21 patients with relapsed or refractory neuroblastoma. They received up to 8 sub-cutaneous 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 cases and bone pain in 1. Injection-site biopsies revealed increased cellularity due to infiltration of CD4+ and CD8+ lymphocytes, eosinophils and Langerhans cells. Systemically, the vaccine produced a 2-fold (P=0.035) expansion of CD4+ T-cells, a 3.5-fold (P=0.039) expansion of NK cells, a 2.1-fold (P=0.014) expansion of eosinophils and a 1.6-fold (P=0.049) 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=0.02) of Th2-type CD3+IL-4+ cells. Supernatant collected from restimulated cells showed increased amounts of IL-4 (11.4-fold, P=0.021) and IL-5 (8.7-fold, P=0.002). Six patients had a significant increase in NK cytolytic activity. Fifteen patients made IgG antibodies that bound to the immunizing cell line. Measurable tumor responses included complete remissions in 2 patients and a partial response in 1. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Zheng, W. Jing, and R. J. Orentas Discovery of YB-1 as a new immunological target in neuroblastoma by vaccination in the context of regulatory T cell blockade Acta Biochim Biophys Sin, November 12, 2009; (2009) gmp092v1. [Abstract] [Full Text] [PDF] X. Yan, B. D. Johnson, and R. J. Orentas Induction of a VLA-2 (CD49b)-Expressing Effector T Cell Population by a Cell-Based Neuroblastoma Vaccine Expressing CD137L J. Immunol., October 1, 2008; 181(7): 4621 - 4631. [Abstract] [Full Text] [PDF] R. F. Rousseau, E. Biagi, A. Dutour, E. S. Yvon, M. P. Brown, T. Lin, Z. Mei, B. Grilley, E. Popek, H. E. Heslop, et al. Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation Blood, February 15, 2006; 107(4): 1332 - 1341. [Abstract] [Full Text] [PDF] E. Biagi, R. Rousseau, E. Yvon, M. Schwartz, G. Dotti, A. Foster, D. Havlik-Cooper, B. Grilley, A. Gee, K. Baker, et al. 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