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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3596-3604. Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-07-2890. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2890v1 105/9/3596    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 Muraro, S. Articles by Bonini, C. Search for Related Content PubMed PubMed Citation Articles by Muraro, S. Articles by Bonini, C. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Molecular modification of idiotypes from B-cell lymphomas for expression in mature dendritic cells as a strategy to induce tumor-reactive CD4+ and CD8+ T-cell responses Sara Muraro, Attilio Bondanza, Matteo Bellone, Philip D. Greenberg, and Chiara Bonini From the Cancer Immunotherapy and Gene Therapy Program, S. Raffaele Scientific Institute, Milano, Italy; the International PhD Program in Molecular Medicine, University "Vita e Salute" Milano, Italy; the Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington; and the Department of Immunology and Medicine, University of Washington, Seattle. Most non-Hodgkin B-cell lymphomas (NHLs) are characterized by the clonal expansion of a single cell expressing a unique rearranged immunoglobulin gene. This idiotype (Id) is a tumor-specific antigen that can be immunologically targeted. The therapeutic efficacy of Id-based vaccines correlates best with detection of cellular immune responses, although these have not been as well characterized as the humoral responses. This study exploited a molecular approach to modify the Id of 38C13 lymphoma for processing via class I and II antigen-processing pathways and evaluated protein expression in dendritic cells (DCs) to simultaneously stimulate tumor reactive CD8+ and CD4+ lymphocytes. Recombinant vaccinia viruses (rVVs) were constructed, coding for Id fused with the targeting signal of the lysosomal-associated membrane protein1 (Id-LAMP1) to promote antigen presentation in the context of major histocompatibility complex (MHC) class II. Mature DCs infected with rVV/Id-LAMP1 elicited both CD4+ and CD8+ Id-specific T cells and protected animals from tumor challenge. Id-specific CD8+ cells were required to mediate the effector phase of a therapeutic response, and CD4+ cells were beneficial in the induction phase of the response. These results demonstrate that fusing Id to LAMP1 enhances CD8+ and CD4+ Id-specific responses for NHLs and may be useful therapeutically. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K.-C. Chang, G.-C. Huang, D. Jones, and Y.-H. Lin Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses Clin. Cancer Res., November 15, 2007; 13(22): 6666 - 6672. [Abstract] [Full Text] [PDF] S. Liu, B. A. Foster, T. Chen, G. Zheng, and A. Chen Modifying Dendritic Cells via Protein Transfer for Antitumor Therapeutics Clin. Cancer Res., January 1, 2007; 13(1): 283 - 291. [Abstract] [Full Text] [PDF]

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