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Blood, 9 April 2009, Vol. 113, No. 15, pp. 3546-3552. Prepublished online as a Blood First Edition Paper on October 21, 2008; DOI 10.1182/blood-2008-07-170274. This Article Full Text (PDF) All Versions of this Article: blood-2008-07-170274v1 113/15/3546    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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 30, 2008 Accepted September 28, 2008 T cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy Roch Houot and Ronald Levy* Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, United States * Corresponding author; email: levy{at}stanford.edu. We have previously shown that intratumoral injection of CpG oligodeoxynucleotide plus systemic chemotherapy can induce a T cell immune response against lymphoma and serve as a therapeutic vaccine to cure tumors in a murine model. Here, we demonstrate that antibody-mediated modulation of T cells increases the efficacy of CpG vaccination, thereby eliminating the need for chemotherapy. T cell modulation was accomplished by targeting both effector and regulatory T cell populations using systemic administration of monoclonal antibodies against OX40, CTLA4, GITR, and Folate Receptor 4 (FR4). Each of these antibodies enhanced the effect of intratumoral CpG. Some pairwise combinations of these antibodies potentiated T cell modulation and further enhanced the efficacy of CpG vaccination. Specifically, the combination of anti-OX40 and anti-CTLA4 which enhance activation and block cell-intrinsic negative regulatory circuits in T cells, respectively, was especially potent. When combined with intratumoral CpG, it induced anti-tumor CD4 and CD8 T cell immunity, cured large and systemic lymphoma tumors without chemotherapy, and provided long-lasting immunity against tumor re-challenge. Our results show that the combination of intratumoral CpG and immunomodulatory T cell antibodies has promise for therapeutic vaccination against lymphoma. These reagents are becoming available for human clinical trials. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. G. Ramsay, A. J. Clear, G. Kelly, R. Fatah, J. Matthews, F. MacDougall, T. A. Lister, A. M. Lee, M. Calaminici, and J. G. Gribben Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy Blood, November 19, 2009; 114(21): 4713 - 4720. [Abstract] [Full Text] [PDF] R. Houot, M. J. Goldstein, H. E. Kohrt, J. H. Myklebust, A. A. Alizadeh, J. T. Lin, J. M. Irish, J. A. Torchia, A. Kolstad, L. Chen, et al. Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion Blood, October 15, 2009; 114(16): 3431 - 3438. [Abstract] [Full Text] [PDF] A. E. Seif, D. M. Barrett, M. Milone, V. I. Brown, S. A. Grupp, and G. S. D. Reid Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses Blood, September 17, 2009; 114(12): 2459 - 2466. [Abstract] [Full Text] [PDF]

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