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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-09-2828. This Article Full Text (PDF) All Versions of this Article: 2002-09-2828v1 102/4/1435    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 Hayashi, T. Articles by Anderson, K. C Search for Related Content PubMed PubMed Citation Articles by Hayashi, T. Articles by Anderson, K. C Social Bookmarking                   What's this? Submitted September 18, 2002 Accepted April 18, 2003 Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes Toshiaki Hayashi, Teru Hideshima, Masaharu Akiyama, Noopur Raje, Paul Richardson, Dharminder Chauhan, and Kenneth C Anderson* Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA * Corresponding author; email: kenneth_anderson{at}dfci.harvard.edu. Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by immunosuppression. In this study, we identified factors in patients' bone marrow (BM) sera inhibiting autologous anti-MM immunity, and developed an ex vivo strategy for inducing MM-specific cytotoxic T lymphocytes (CTLs). We found that sera from BM of MM patients inhibited induction of dendritic cells (DCs), evidenced by both phenotype and only weak stimulation of T cell proliferation. Anti-VEGF and/or anti-IL-6 antibodies neutralized this inhibitory effect, confirming that VEGF and IL-6, at least in part, mediate immunosuppression in MM patients. To induce MM-specific CTLs ex vivo, immature DCs were generated by culture of adherent mononuclear cells in medium containing GM-CSF and IL-4 for 5 days, and then cocultured with apoptotic MM bodies in the presence of TNF- for 3 days to induce their maturation. Autologous BM or peripheral blood mononuclear cells were stimulated weekly with these DCs, and cytotoxicity was examined against the MM cells used to pulse DCs. DCs cultured with apoptotic bodies stimulated significantly greater T cell proliferation (stimulation index (SI) = 23.2 at T: DC of 360:1) than T cells stimulated by MM cells only (SI = 5.6), DCs only (SI = 9.3), or MM lysate-pulsed DCs (SI = 13.5). These CTLs from MM patients demonstrated specific cytotoxicity (24.7% at E:T of 40:1) against autologous primary MM cells. These studies therefore show that CTLs from MM patients can recognize and lyse autologous tumor cells and provide the framework for novel immunotherapy to improve patient outcome in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Cohen, J. Haimovich, and N. Hollander Dendritic Cell-Based Therapeutic Vaccination against Myeloma: Vaccine Formulation Determines Efficacy against Light Chain Myeloma J. Immunol., February 1, 2009; 182(3): 1667 - 1673. [Abstract] [Full Text] [PDF] E. Alici, T. Sutlu, B. Bjorkstrand, M. Gilljam, B. Stellan, H. Nahi, H. C. Quezada, G. Gahrton, H.-G. Ljunggren, and M. S. Dilber Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components Blood, March 15, 2008; 111(6): 3155 - 3162. [Abstract] [Full Text] [PDF] A. Jalili, S. Ozaki, T. Hara, H. Shibata, T. Hashimoto, M. Abe, Y. Nishioka, and T. 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