SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on March 6, 2003; DOI 10.1182/blood-2002-12-3665. This Article 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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted December 4, 2002 Accepted February 20, 2003 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 Medizinische Poliklinik, University of Wuerzburg, Wuerzburg, Germany Lehrstuhl fuer Lebensmittelchemie, University of Wuerzburg, Wuerzburg, Germany Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany * Corresponding author; email: kunzmann_v{at}medizin.uni-wuerzburg.de. There is increasing evidence that T cells have potent innate anti-tumor activity. We described previously that synthetic aminobisphosphonates are potent gd T cell stimulatory compounds which induce cytokine secretion (i. e. IFN-) and cell-mediated cytotoxicity against lymphoma and myeloma cell lines in vitro. To evaluate the anti-tumor activity of T cells in vivo, we initiated a pilot study of low dose 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 anti-lymphoma efficacy of the combination of pamidronate and IL-2. The first ten patients (cohort A) who entered the study received 90mg pamidronate intravenously (IV) on day 1 followed by increasing dose levels of continuous 24-hour IV infusions of IL-2 (0.25 - 3 x 106 IU/m2) from day 3-8. 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 nine 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 anti-lymphoma 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: T cells in cancer immunotherapy Jack F. Bukowski Blood 2003 102: 4. [Full Text] [PDF] This article has been cited by other articles: E. Terpos, O. Sezer, P. I. Croucher, R. Garcia-Sanz, M. Boccadoro, J. San Miguel, J. Ashcroft, J. Blade, M. Cavo, M. Delforge, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network Ann. Onc., August 1, 2009; 20(8): 1303 - 1317. [Abstract] [Full Text] [PDF] J. Li, M. J. Herold, B. Kimmel, I. Muller, B. Rincon-Orozco, V. Kunzmann, and T. Herrmann Reduced Expression of the Mevalonate Pathway Enzyme Farnesyl Pyrophosphate Synthase Unveils Recognition of Tumor Cells by V{gamma}9V{delta}2 T Cells J. Immunol., June 15, 2009; 182(12): 8118 - 8124. [Abstract] [Full Text] [PDF] M. Todaro, M. D'Asaro, N. Caccamo, F. Iovino, M. G. Francipane, S. Meraviglia, V. Orlando, C. La Mendola, G. Gulotta, A. Salerno, et al. Efficient Killing of Human Colon Cancer Stem Cells by {gamma}{delta} T Lymphocytes J. Immunol., June 1, 2009; 182(11): 7287 - 7296. [Abstract] [Full Text] [PDF] J. Gertner-Dardenne, C. Bonnafous, C. Bezombes, A.-H. Capietto, V. Scaglione, S. Ingoure, D. Cendron, E. Gross, J.-F. Lepage, A. Quillet-Mary, et al. Bromohydrin pyrophosphate enhances antibody-dependent cell-mediated cytotoxicity induced by therapeutic antibodies Blood, May 14, 2009; 113(20): 4875 - 4884. [Abstract] [Full Text] [PDF] C. Devaud, E. Bilhere, S. Loizon, V. Pitard, C. Behr, J.-F. Moreau, J. Dechanet-Merville, and M. Capone Antitumor Activity of {gamma}{delta} T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model Cancer Res., May 1, 2009; 69(9): 3971 - 3978. [Abstract] [Full Text] [PDF] A. Thedrez, C. Harly, A. Morice, S. Salot, M. Bonneville, and E. Scotet IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory Responses of Human V{gamma}9V{delta}2 T Cells for Adoptive Immunotherapy J. Immunol., March 15, 2009; 182(6): 3423 - 3431. [Abstract] [Full Text] [PDF] J. D. French, C. L. Roark, W. K. Born, and R. L. O'Brien {gamma}{delta} T Lymphocyte Homeostasis Is Negatively Regulated by {beta}2-Microglobulin J. Immunol., February 15, 2009; 182(4): 1892 - 1900. [Abstract] [Full Text] [PDF] N. L. Bryant, C. Suarez-Cuervo, G. Y. Gillespie, J. M. Markert, L. B. Nabors, S. Meleth, R. D. Lopez, and L. S. Lamb Jr. Characterization and immunotherapeutic potential of {gamma}{delta} T-cells in patients with glioblastoma Neuro-oncol, January 1, 2009; 11(4): 357 - 367. [Abstract] [Full Text] [PDF] C. Agrati, E. Cimini, A. Sacchi, V. Bordoni, C. Gioia, R. Casetti, F. Turchi, M. Tripodi, and F. Martini Activated V{gamma}9V{delta}2 T Cells Trigger Granulocyte Functions via MCP-2 Release J. Immunol., January 1, 2009; 182(1): 522 - 529. [Abstract] [Full Text] [PDF] G. Sarikonda, H. Wang, K.-J. Puan, X.-h. Liu, H. K. Lee, Y. Song, M. D. Distefano, E. Oldfield, G. D. Prestwich, and C. T. Morita Photoaffinity Antigens for Human {gamma}{delta} T Cells J. Immunol., December 1, 2008; 181(11): 7738 - 7750. [Abstract] [Full Text] [PDF] Z. Liu, I.-E. A. Eltoum, B. Guo, B. H. Beck, G. A. Cloud, and R. D. Lopez Protective Immunosurveillance and Therapeutic Antitumor Activity of {gamma}{delta} T Cells Demonstrated in a Mouse Model of Prostate Cancer J. Immunol., May 1, 2008; 180(9): 6044 - 6053. [Abstract] [Full Text] [PDF] M. Takahara, M. Miyai, M. Tomiyama, M. Mutou, A. J. Nicol, and M. Nieda Copulsing tumor antigen-pulsed dendritic cells with zoledronate efficiently enhance the expansion of tumor antigen-specific CD8+ T cells via V{gamma}9{gamma}{delta} T cell activation J. Leukoc. Biol., March 1, 2008; 83(3): 742 - 754. [Abstract] [Full Text] [PDF] D. A. Kosub, G. Lehrman, J. M. Milush, D. Zhou, E. Chacko, A. Leone, S. Gordon, G. Silvestri, J. G. Else, P. Keiser, et al. Gamma/Delta T-Cell Functional Responses Differ after Pathogenic Human Immunodeficiency Virus and Nonpathogenic Simian Immunodeficiency Virus Infections J. Virol., February 1, 2008; 82(3): 1155 - 1165. [Abstract] [Full Text] [PDF] J. Holderness, L. Jackiw, E. Kimmel, H. Kerns, M. Radke, J. F. Hedges, C. Petrie, P. McCurley, P. M. Glee, A. Palecanda, et al. Select Plant Tannins Induce IL-2R{alpha} Up-Regulation and Augment Cell Division in {gamma}{delta} T Cells J. Immunol., November 15, 2007; 179(10): 6468 - 6478. [Abstract] [Full Text] [PDF] F. Dieli, D. Vermijlen, F. Fulfaro, N. Caccamo, S. Meraviglia, G. Cicero, A. Roberts, S. Buccheri, M. D'Asaro, N. Gebbia, et al. Targeting Human {gamma}{delta} T Cells with Zoledronate and Interleukin-2 for Immunotherapy of Hormone-Refractory Prostate Cancer Cancer Res., August 1, 2007; 67(15): 7450 - 7457. [Abstract] [Full Text] [PDF] K.-J. Puan, C. Jin, H. Wang, G. Sarikonda, A. M. Raker, H. K. Lee, M. I. Samuelson, E. Marker-Hermann, L. Pasa-Tolic, E. Nieves, et al. Preferential recognition of a microbial metabolite by human V{gamma}2V{delta}2 T cells Int. Immunol., May 1, 2007; 19(5): 657 - 673. [Abstract] [Full Text] [PDF] S. Catellani, A. Poggi, A. Bruzzone, P. Dadati, J. L. Ravetti, M. Gobbi, and M. R. Zocchi Expansion of V{delta}1 T lymphocytes producing IL-4 in low-grade non-Hodgkin lymphomas expressing UL-16-binding proteins Blood, March 1, 2007; 109(5): 2078 - 2085. [Abstract] [Full Text] [PDF] K. Thompson and M. J. Rogers Bisphosphonates and {gamma}{delta} T-Cells: New Insights into Old Drugs IBMS BoneKEy, August 1, 2006; 3(8): 5 - 13. [Abstract] [Full Text] [PDF] L. T. van der Veken, R. S. Hagedoorn, M. M. van Loenen, R. Willemze, J.H. F. Falkenburg, and M. H.M. Heemskerk {alpha}{beta} T-Cell Receptor Engineered {gamma}{delta} T Cells Mediate Effective Antileukemic Reactivity. Cancer Res., March 15, 2006; 66(6): 3331 - 3337. [Abstract] [Full Text] [PDF] C. Agrati, T. Alonzi, R. De Santis, C. Castilletti, I. Abbate, M. R. Capobianchi, G. D'Offizi, F. Siepi, G. M. Fimia, M. Tripodi, et al. Activation of V{gamma}9V{delta}2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication Int. Immunol., January 1, 2006; 18(1): 11 - 18. [Abstract] [Full Text] [PDF] L. Gao, H. Deng, H. Zhao, A. Hirbe, J. Harding, L. Ratner, and K. Weilbaecher HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition Blood, December 15, 2005; 106(13): 4294 - 4302. [Abstract] [Full Text] [PDF] M. Otto, R. C. Barfield, W. J. Martin, R. Iyengar, W. Leung, T. Leimig, S. Chaleff, S. D. Gillies, and R. Handgretinger Combination Immunotherapy with Clinical-Scale Enriched Human {gamma}{delta} T cells, hu14.18 Antibody, and the Immunocytokine Fc-IL7 in Disseminated Neuroblastoma Clin. Cancer Res., December 1, 2005; 11(23): 8486 - 8491. [Abstract] [Full Text] [PDF] W. L. Havran The Biology of {gamma}{delta} T Cells: What Is the Relationship between {gamma}{delta} T Cells and Cancer? Will an Increased Number and/or Function of {gamma}{delta} T Cells Result in Lower Cancer Incidence? J. Nutr., December 1, 2005; 135(12): 2909S - 2909S. [Full Text] [PDF] H. Sicard, S. Ingoure, B. Luciani, C. Serraz, J.-J. Fournie, M. Bonneville, J. Tiollier, and F. Romagne In Vivo Immunomanipulation of V{gamma}9V{delta}2 T Cells with a Synthetic Phosphoantigen in a Preclinical Nonhuman Primate Model J. Immunol., October 15, 2005; 175(8): 5471 - 5480. [Abstract] [Full Text] [PDF] M. Corvaisier, A. Moreau-Aubry, E. Diez, J. Bennouna, J.-F. Mosnier, E. Scotet, M. Bonneville, and F. Jotereau V{gamma}9V{delta}2 T Cell Response to Colon Carcinoma Cells J. Immunol., October 15, 2005; 175(8): 5481 - 5488. [Abstract] [Full Text] [PDF] J. D. French, C. L. Roark, W. K. Born, and R. L. O'Brien {gamma}{delta} T cell homeostasis is established in competition with {alpha}{beta} T cells and NK cells PNAS, October 11, 2005; 102(41): 14741 - 14746. [Abstract] [Full Text] [PDF] S. Girlanda, C. Fortis, D. Belloni, E. Ferrero, P. Ticozzi, C. Sciorati, M. Tresoldi, A. Vicari, T. Spies, V. Groh, et al. MICA Expressed by Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance Plasma Cells Costimulates Pamidronate-Activated {gamma}{delta} Lymphocytes Cancer Res., August 15, 2005; 65(16): 7502 - 7508. [Abstract] [Full Text] [PDF] B. Rincon-Orozco, V. Kunzmann, P. Wrobel, D. Kabelitz, A. Steinle, and T. Herrmann Activation of V{gamma}9V{delta}2 T Cells by NKG2D J. Immunol., August 15, 2005; 175(4): 2144 - 2151. [Abstract] [Full Text] [PDF] R. Casetti, G. Perretta, A. Taglioni, M. Mattei, V. Colizzi, F. Dieli, G. D'Offizi, M. Malkovsky, and F. Poccia Drug-Induced Expansion and Differentiation of V{gamma}9V{delta}2 T Cells In Vivo: The Role of Exogenous IL-2 J. Immunol., August 1, 2005; 175(3): 1593 - 1598. [Abstract] [Full Text] [PDF] C. Munz, R. M. Steinman, and S.-i. Fujii Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity J. Exp. Med., July 18, 2005; 202(2): 203 - 207. [Abstract] [Full Text] [PDF] P. Clezardin, F. H. Ebetino, and P. G.J. Fournier Bisphosphonates and Cancer-Induced Bone Disease: Beyond Their Antiresorptive Activity Cancer Res., June 15, 2005; 65(12): 4971 - 4974. [Abstract] [Full Text] [PDF] F. Halary, V. Pitard, D. Dlubek, R. Krzysiek, H. de la Salle, P. Merville, C. Dromer, D. Emilie, J.-F. Moreau, and J. Dechanet-Merville Shared reactivity of V{delta}2neg {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells J. Exp. Med., May 16, 2005; 201(10): 1567 - 1578. [Abstract] [Full Text] [PDF] E. Viey, G. Fromont, B. Escudier, Y. Morel, S. Da Rocha, S. Chouaib, and A. Caignard Phosphostim-Activated {gamma}{delta} T Cells Kill Autologous Metastatic Renal Cell Carcinoma J. Immunol., February 1, 2005; 174(3): 1338 - 1347. [Abstract] [Full Text] [PDF] M. Poupot, F. Pont, and J.-J. Fournie Profiling Blood Lymphocyte Interactions with Cancer Cells Uncovers the Innate Reactivity of Human {gamma}{delta} T Cells to Anaplastic Large Cell Lymphoma J. Immunol., February 1, 2005; 174(3): 1717 - 1722. [Abstract] [Full Text] [PDF] D. Kabelitz, D. Wesch, E. Pitters, and M. Zoller Characterization of Tumor Reactivity of Human V{gamma}9V{delta}2 {gamma}{delta} T Cells In Vitro and in SCID Mice In Vivo J. Immunol., December 1, 2004; 173(11): 6767 - 6776. [Abstract] [Full Text] [PDF] D. F. Angelini, G. Borsellino, M. Poupot, A. Diamantini, R. Poupot, G. Bernardi, F. Poccia, J.-J. Fournie, and L. Battistini Fc{gamma}RIII discriminates between 2 subsets of V{gamma}9V{delta}2 effector cells with different responses and activation pathways Blood, September 15, 2004; 104(6): 1801 - 1807. [Abstract] [Full Text] [PDF] J. N. Blattman and P. D. Greenberg Cancer Immunotherapy: A Treatment for the Masses Science, July 9, 2004; 305(5681): 200 - 205. [Abstract] [Full Text] [PDF] F. Dieli, N. Gebbia, F. Poccia, N. Caccamo, C. Montesano, F. Fulfaro, C. Arcara, M. R. Valerio, S. Meraviglia, C. Di Sano, et al. Induction of {gamma}{delta} T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo Blood, September 15, 2003; 102(6): 2310 - 2311. [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020