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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 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 Citation Map 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. Related Collections Immunobiology Clinical Trials and Observations Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1718-1726 GENE THERAPY 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, and Douglas Strother From the Center for Cell and Gene Therapy, Texas Children's Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX; and the Department of Hematology-Oncology, Department of Surgery, St Jude Children's Research Hospital, Memphis, TN. 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. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. Responses to Human CD40 Ligand/Human Interleukin-2 Autologous Cell Vaccine in Patients with B-Cell Chronic Lymphocytic Leukemia Clin. Cancer Res., October 1, 2005; 11(19): 6916 - 6923. [Abstract] [Full Text] [PDF] E. Lavergne, C. Combadiere, M. Iga, A. Boissonnas, O. Bonduelle, M. Maho, P. Debre, and B. Combadiere Intratumoral CC Chemokine Ligand 5 Overexpression Delays Tumor Growth and Increases Tumor Cell Infiltration J. Immunol., September 15, 2004; 173(6): 3755 - 3762. [Abstract] [Full Text] [PDF] B. H. Kushner Neuroblastoma: A Disease Requiring a Multitude of Imaging Studies J. Nucl. Med., July 1, 2004; 45(7): 1172 - 1188. [Abstract] [Full Text] [PDF] F. C. Peterson, E. S. Elgin, T. J. Nelson, F. Zhang, T. J. Hoeger, R. J. Linhardt, and B. F. Volkman Identification and Characterization of a Glycosaminoglycan Recognition Element of the C Chemokine Lymphotactin J. Biol. Chem., March 26, 2004; 279(13): 12598 - 12604. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020