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Blood, 15 October 2009, Vol. 114, No. 16, pp. 3431-3438. Prepublished online as a Blood First Edition Paper on July 29, 2009; DOI 10.1182/blood-2009-05-223958. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2009-05-223958v1 114/16/3431    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 Houot, R. Articles by Levy, R. Search for Related Content PubMed PubMed Citation Articles by Houot, R. Articles by Levy, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 26, 2009 Accepted July 19, 2009 Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion Roch Houot, Matthew J. Goldstein, Holbrook E. Kohrt, June H. Myklebust, Ash A. Alizadeh, Jack T. Lin, Jonathan M. Irish, James A. Torchia, Arne Kolstad, Lieping Chen, and Ronald Levy* Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, United States Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, CA, United States Department of Oncology, Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States * Corresponding author; email: levy{at}stanford.edu. Despite the success of passive immunotherapy with monoclonal antibodies (mAbs), many lymphoma patients eventually relapse. Induction of an adaptive immune response may elicit active and long-lasting antitumor immunity, thereby preventing or delaying recurrence. Immunomodulating mAbs directed against immune cell targets can be used to enhance the immune response in order to achieve efficient antitumor immunity. Anti-CD137 agonistic mAb has demonstrated antitumor efficacy in various tumor models and has now entered clinical trials for the treatment of solid tumors. Here, we investigate the therapeutic potential of anti-CD137 mAb in lymphoma. We found that human primary lymphoma tumors are infiltrated with CD137+ T cells. We therefore hypothesized that lymphoma would be susceptible to treatment with anti-CD137 agonistic mAb. Using a mouse model, we demonstrate that anti-CD137 therapy has potent anti-lymphoma activity in vivo. The antitumor effect of anti-CD137 therapy was mediated by both NK and CD8 T cells and induced long-lasting immunity. Moreover, the antitumor activity of anti-CD137 mAb could be further enhanced by depletion of Treg cells. These results support the evaluation of anti-CD137 therapy in clinical trials for patients with lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The doctor's dilemma: stimulating T cells Mark Vickers Blood 2009 114: 3361-3362. [Full Text] [PDF] This article has been cited by other articles: M. Vickers The doctor's dilemma: stimulating T cells Blood, October 15, 2009; 114(16): 3361 - 3362. [Full Text] [PDF]

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