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Prepublished online as a Blood First Edition Paper on March 6, 2003; DOI 10.1182/blood-2002-12-3665. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3665v1 102/1/200    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 Wilhelm, M. Articles by Tony, H.-P. Search for Related Content PubMed PubMed Citation Articles by Wilhelm, M. Articles by Tony, H.-P. Related Collections Immunobiology Immunotherapy Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 200-206 IMMUNOBIOLOGY T cells for immune therapy of patients with lymphoid malignancies Martin Wilhelm, Volker Kunzmann, Susanne Eckstein, Peter Reimer, Florian Weissinger, Thomas Ruediger, and Hans-Peter Tony From the Medizinische Poliklinik Wuerzburg, University of Wuerzburg, Germany; Lehrstuhl fuer Lebensmittelchemie, University of Wuerzburg, Germany; and Institute of Pathology, University of Wuerzburg, Germany. There is increasing evidence that T cells have potent innate antitumor activity. We described previously that synthetic aminobisphosphonates are potent T cell stimulatory compounds that induce cytokine secretion (ie, interferon [IFN-]) and cell-mediated cytotoxicity against lymphoma and myeloma cell lines in vitro. To evaluate the antitumor activity of T cells in vivo, we initiated a pilot study of low-dose interleukin 2 (IL-2) in combination with pamidronate in 19 patients with relapsed/refractory low-grade non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). The objectives of this trial were to determine toxicity, the most effective dose for in vivo activation/proliferation of T cells, and antilymphoma efficacy of the combination of pamidronate and IL-2. The first 10 patients (cohort A) who entered the study received 90 mg pamidronate intravenously on day 1 followed by increasing dose levels of continuous 24-hour intravenous (IV) infusions of IL-2 (0.25 to 3 x 106 IU/m2) from day 3 to day 8. Even at the highest IL-2 dose level in vivo, T-cell activation/proliferation and response to treatment were disappointing with only 1 patient achieving stable disease. Therefore, the next 9 patients were selected by positive in vitro proliferation of T cells in response to pamidronate/IL-2 and received a modified treatment schedule (6-hour bolus IV IL-2 infusions from day 1-6). In this patient group (cohort B), significant in vivo activation/proliferation of T cells was observed in 5 patients (55%), and objective responses (PR) were achieved in 3 patients (33%). Only patients with significant in vivo proliferation of T cells responded to treatment, indicating that T cells might contribute to this antilymphoma effect. Overall, administration of pamidronate and low-dose IL-2 was well tolerated. In conclusion, this clinical trial demonstrates, for the first time, that T-cell–mediated immunotherapy is feasible and can induce objective tumor responses. (Blood. 2003;102:200-206) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: T cells in cancer immunotherapy Jack F. 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