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Tumor Rejection by in Vivo Administration of Anti-CD25 (Interleukin-2 Receptor ) Monoclonal Antibody¹

Department of Parasitology and Immunology, Okayama University Medical School, Okayama 700-8558 [S. O., I. T., E. N.]; Department of Oncology, Nagasaki University School of Medicine, Nagasaki 852-8523 [S. O.]; Department of Immunopathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015 [J. S., S. S.]; and Department of Biochemistry, Fukushima Medical College, Fukushima 960-1295 [T. F.], Japan

Immune regulation has been shown to be involved in the progressive growth of some murine tumors. In this study, we demonstrated that a single in vivo administration of an amount less than 0.125 mg of anti-CD25 interleukin 2 receptor monoclonal antibody (mAb; PC61) caused the regression of tumors that grew progressively in syngeneic mice. The tumors used were five leukemias, a myeloma, and two sarcomas derived from four different inbred mouse strains. Anti-CD25 mAb (PC61) showed an effect in six of the eight tumors. Administration of anti-CD25 mAb (PC61) caused a reduction in the number of CD4⁺CD25⁺ cells in the peripheral lymphoid tissues. The findings suggested that CD4⁺CD25⁺ immunoregulatory cells were involved in the growth of those tumors. Kinetic analysis showed that the administration of anti-CD25 mAb (PC61) later than day 2 after tumor inoculation caused no tumor regression, irrespective of depletion of CD4⁺CD25⁺ immunoregulatory cells. Two leukemias, on which the PC61-treatment had no effect, seemed to be incapable of eliciting effective rejection responses in the recipient mice because of low or no antigenicity.

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				H. Nishikawa, F. Qian, T. Tsuji, G. Ritter, L. J. Old, S. Gnjatic, and K. Odunsi Influence of CD4+CD25+ Regulatory T Cells on Low/High-Avidity CD4+ T Cells following Peptide Vaccination J. Immunol., May 15, 2006; 176(10): 6340 - 6346. [Abstract] [Full Text] [PDF]

				M. Beyer, M. Kochanek, T. Giese, E. Endl, M. R. Weihrauch, P. A. Knolle, S. Classen, and J. L. Schultze In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma Blood, May 15, 2006; 107(10): 3940 - 3949. [Abstract] [Full Text] [PDF]

				O. Saitoh and Y. Nagayama Regulation of Graves' Hyperthyroidism with Naturally Occurring CD4+CD25+ Regulatory T Cells in a Mouse Model Endocrinology, May 1, 2006; 147(5): 2417 - 2422. [Abstract] [Full Text] [PDF]

				Z.-Z. Yang, A. J. Novak, M. J. Stenson, T. E. Witzig, and S. M. Ansell Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma Blood, May 1, 2006; 107(9): 3639 - 3646. [Abstract] [Full Text] [PDF]

				G. Lizee, L. G. Radvanyi, W. W. Overwijk, and P. Hwu Immunosuppression in melanoma immunotherapy: potential opportunities for intervention. Clin. Cancer Res., April 1, 2006; 12(7): 2359s - 2365s. [Abstract] [Full Text] [PDF]

				A. P. Kohm, J. S. McMahon, J. R. Podojil, W. S. Begolka, M. DeGutes, D. J. Kasprowicz, S. F. Ziegler, and S. D. Miller Cutting Edge: Anti-CD25 Monoclonal Antibody Injection Results in the Functional Inactivation, Not Depletion, of CD4+CD25+ T Regulatory Cells J. Immunol., March 15, 2006; 176(6): 3301 - 3305. [Abstract] [Full Text] [PDF]

				J. Taieb, N. Chaput, N. Schartz, S. Roux, S. Novault, C. Menard, F. Ghiringhelli, M. Terme, A. F. Carpentier, G. Darrasse-Jese, et al. Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J. Immunol., March 1, 2006; 176(5): 2722 - 2729. [Abstract] [Full Text] [PDF]

				H. Geng, G.-M. Zhang, D. Li, H. Zhang, Y. Yuan, H.-G. Zhu, H. Xiao, L.-F. Han, and Z.-H. Feng Soluble Form of T Cell Ig Mucin 3 Is an Inhibitory Molecule in T Cell-Mediated Immune Response J. Immunol., February 1, 2006; 176(3): 1411 - 1420. [Abstract] [Full Text] [PDF]

				M. J. Smyth, M. W. L. Teng, J. Swann, K. Kyparissoudis, D. I. Godfrey, and Y. Hayakawa CD4+CD25+ T Regulatory Cells Suppress NK Cell-Mediated Immunotherapy of Cancer J. Immunol., February 1, 2006; 176(3): 1582 - 1587. [Abstract] [Full Text] [PDF]

				A. Comes, O. Rosso, A. M. Orengo, E. Di Carlo, C. Sorrentino, R. Meazza, T. Piazza, B. Valzasina, P. Nanni, M. P. Colombo, et al. CD25+ Regulatory T Cell Depletion Augments Immunotherapy of Micrometastases by an IL-21-Secreting Cellular Vaccine J. Immunol., February 1, 2006; 176(3): 1750 - 1758. [Abstract] [Full Text] [PDF]

				S. Chattopadhyay, S. Mehrotra, A. Chhabra, U. Hegde, B. Mukherji, and N. G. Chakraborty Effect of CD4+CD25+ and CD4+CD25- T Regulatory Cells on the Generation of Cytolytic T Cell Response to a Self but Human Tumor-Associated Epitope In Vitro J. Immunol., January 15, 2006; 176(2): 984 - 990. [Abstract] [Full Text] [PDF]

				M. Terabe, J. Swann, E. Ambrosino, P. Sinha, S. Takaku, Y. Hayakawa, D. I. Godfrey, S. Ostrand-Rosenberg, M. J. Smyth, and J. A. Berzofsky A nonclassical non-V{alpha}14J{alpha}18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance J. Exp. Med., December 19, 2005; 202(12): 1627 - 1633. [Abstract] [Full Text] [PDF]

				A. S.I. Loskog, M. E. Fransson, and T. T.H. Totterman AdCD40L Gene Therapy Counteracts T Regulatory Cells and Cures Aggressive Tumors in an Orthotopic Bladder Cancer Model Clin. Cancer Res., December 15, 2005; 11(24): 8816 - 8821. [Abstract] [Full Text] [PDF]

				A. Liu, P. Hu, L. A. Khawli, and A. L. Epstein Combination B7-Fc Fusion Protein Treatment and Treg Cell Depletion Therapy Clin. Cancer Res., December 1, 2005; 11(23): 8492 - 8502. [Abstract] [Full Text] [PDF]

				Y.-Q. Chen, H.-Z. Shi, X.-J. Qin, W.-N. Mo, X.-D. Liang, Z.-X. Huang, H.-B. Yang, and C. Wu CD4+CD25+ Regulatory T Lymphocytes in Malignant Pleural Effusion Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1434 - 1439. [Abstract] [Full Text] [PDF]

				L. E. Raez, S. Fein, and E. R. Podack Lung Cancer Immunotherapy Clin. Med. Res., November 1, 2005; 3(4): 221 - 228. [Abstract] [Full Text] [PDF]

				M. Boudewijns, A. Jeurissen, M. Wuyts, L. Moens, L. Boon, J. J. Van Neerven, A. Kasran, L. Overbergh, C. Lenaerts, M. Waer, et al. Blockade of CTLA-4 (CD152) enhances the murine antibody response to pneumococcal capsular polysaccharides J. Leukoc. Biol., November 1, 2005; 78(5): 1060 - 1069. [Abstract] [Full Text] [PDF]

				F. Ghiringhelli, C. Menard, M. Terme, C. Flament, J. Taieb, N. Chaput, P. E. Puig, S. Novault, B. Escudier, E. Vivier, et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-{beta}-dependent manner J. Exp. Med., October 17, 2005; 202(8): 1075 - 1085. [Abstract] [Full Text] [PDF]

				K. Ko, S. Yamazaki, K. Nakamura, T. Nishioka, K. Hirota, T. Yamaguchi, J. Shimizu, T. Nomura, T. Chiba, and S. Sakaguchi Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells J. Exp. Med., October 3, 2005; 202(7): 885 - 891. [Abstract] [Full Text] [PDF]

				Z. Fehervari and S. Sakaguchi CD4+ regulatory cells as a potential immunotherapy Phil Trans R Soc B, September 29, 2005; 360(1461): 1647 - 1661. [Abstract] [Full Text] [PDF]

				S. P Cobbold T cell tolerance induced by therapeutic antibodies Phil Trans R Soc B, September 29, 2005; 360(1461): 1695 - 1705. [Abstract] [Full Text] [PDF]