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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-03-0991. This Article Full Text (PDF) All Versions of this Article: 2002-03-0991v1 101/2/568    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 Curti, A. Articles by Colombo, M. P Search for Related Content PubMed PubMed Citation Articles by Curti, A. Articles by Colombo, M. P Social Bookmarking                   What's this? Submitted April 1, 2002 Accepted August 5, 2002 Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma Antonio Curti, Mariella Parenza, and Mario P Colombo* Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy * Corresponding author; email: mcolombo{at}istitutotumori.mi.it. Cytokine gene-modified tumor cells have increased immunogenicity and retain the antigenic repertoire of a particular neoplasia. However, practical concerns have led to an increased interest in allogeneic gene-transduced bystander cells as a broader source of cytokines for autologous tumor cell-based vaccines. Here, we show that allogeneic B78H1 MHC class I- negative and positive (H-2Kb and Db transfected) cells induced CTL and protection in BALB/c mice at comparable levels in response to a challenge with C26 (H2d) colon carcinoma cells sharing the tumor-associated antigen env-gp70 with both cell lines. Class I-negative B78H1 cells transduced to express IL-12 and mixed with autologous A20 tumor cells led to eradication of preestablished A20 lymphoma in 50% or 100% of treated mice after 3 or 4 vaccinations, respectively, whereas A20 cells alone or mixed with non-transduced B78H1 cured none or 50% of mice after 3 or 4 vaccinations, respectively. Immunization with the IL-12-producing bystander cell line increased tumor-specific proliferation and type 1 cytokine production by CD4+ T cells. By contrast, CD4 T-cell function appeared impaired after immunization with A20 cells alone or mixed with B78H1 cells. Indeed, only CD4+ T cells from IL-12-treated mice could be restimulated with anti-OX40 mAb in place of a fourth cellular boost. Moreover, the IL-12-based tumor vaccine induced expansion of tumor-specific IFN--producing CD8+ T cells. These results are clinically relevant for the development of feasible IL-12 cancer vaccines based on engineered class I-negative bystander cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-T. Rubio, Y.-M. Kim, T. Sachs, M. Mapara, G. Zhao, and M. Sykes Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-{gamma} Blood, September 15, 2003; 102(6): 2300 - 2307. [Abstract] [Full Text] [PDF]

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