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Originally published in Science Express on 19 September 2002
Science 25 October 2002:
Vol. 298. no. 5594, pp. 850 - 854
DOI: 10.1126/science.1076514
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Reports

Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes

Mark E. Dudley,1 John R. Wunderlich,1 Paul F. Robbins,1 James C. Yang,1 Patrick Hwu,1 Douglas J. Schwartzentruber,1 Suzanne L. Topalian,1 Richard Sherry,1 Nicholas P. Restifo,1 Amy M. Hubicki,1 Michael R. Robinson,2 Mark Raffeld,3 Paul Duray,3 Claudia A. Seipp,1 Linda Rogers-Freezer,1 Kathleen E. Morton,1 Sharon A. Mavroukakis,1 Donald E. White,1 Steven A. Rosenberg1*

We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases.

1 Surgery Branch, National Cancer Institute;
2 National Eye Institute;
3 Laboratory of Pathology, National Cancer Institute; National Institutes of Health, Bethesda, MD 20902, USA.
*   To whom correspondence should be addressed. E-mail: SAR{at}nih.gov

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S. Landmeier, B. Altvater, S. Pscherer, B. R. Eing, J. Kuehn, C. M. Rooney, H. Juergens, and C. Rossig (2007)
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   Abstract »    Full Text »    PDF »
Decreased Tumor Surveillance after Adoptive T-Cell Therapy.
M. Matter, V. Pavelic, D. D. Pinschewer, S. Mumprecht, B. Eschli, T. Giroglou, D. von Laer, and A. F. Ochsenbein (2007)
Cancer Res. 67, 7467-7476
   Abstract »    Full Text »    PDF »
Cross-Talk between T Cells and Innate Immune Cells Is Crucial for IFN-{gamma}-Dependent Tumor Rejection.
Z. Li, F. Pradera, T. Kammertoens, B. Li, S. Liu, and Z. Qin (2007)
J. Immunol. 179, 1568-1576
   Abstract »    Full Text »    PDF »
In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.
M. J. Pittet, J. Grimm, C. R. Berger, T. Tamura, G. Wojtkiewicz, M. Nahrendorf, P. Romero, F. K. Swirski, and R. Weissleder (2007)
PNAS 104, 12457-12461
   Abstract »    Full Text »    PDF »
Brain Microenvironment Promotes the Final Functional Maturation of Tumor-Specific Effector CD8+ T Cells.
F. Masson, T. Calzascia, W. Di Berardino-Besson, N. de Tribolet, P.-Y. Dietrich, and P. R. Walker (2007)
J. Immunol. 179, 845-853
   Abstract »    Full Text »    PDF »
Immunologic Approaches to Ovarian Cancer Treatment.
P. Sabbatini and K. Odunsi (2007)
J. Clin. Oncol. 25, 2884-2893
   Abstract »    Full Text »    PDF »
Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific antitumor immunity from T-cell populations undergoing homeostatic peripheral expansion after BMT.
J. N. Kochenderfer, J. L. Simpson, C. D. Chien, and R. E. Gress (2007)
Blood 110, 450-460
   Abstract »    Full Text »    PDF »
CD4 cells can be more efficient at tumor rejection than CD8 cells.
A. Perez-Diez, N. T. Joncker, K. Choi, W. F. N. Chan, C. C. Anderson, O. Lantz, and P. Matzinger (2007)
Blood 109, 5346-5354
   Abstract »    Full Text »    PDF »
Signal 3 Availability Limits the CD8 T Cell Response to a Solid Tumor.
J. M. Curtsinger, M. Y. Gerner, D. C. Lins, and M. F. Mescher (2007)
J. Immunol. 178, 6752-6760
   Abstract »    Full Text »    PDF »
Detection and Long-Term In Vivo Monitoring of Individual Tumor-Specific T Cell Clones in Patients with Metastatic Melanoma.
J. Michalek, I. Kocak, V. Fait, J. Zaloudik, and R. Hajek (2007)
J. Immunol. 178, 6789-6795
   Abstract »    Full Text »    PDF »
Human CD5 Protects Circulating Tumor Antigen-Specific CTL from Tumor-Mediated Activation-Induced Cell Death.
G. Friedlein, F. El Hage, I. Vergnon, C. Richon, P. Saulnier, Y. Lecluse, A. Caignard, L. Boumsell, G. Bismuth, S. Chouaib, et al. (2007)
J. Immunol. 178, 6821-6827
   Abstract »    Full Text »    PDF »
Spontaneous tumor rejection by cbl-b-deficient CD8+ T cells.
S. Loeser, K. Loser, M. S. Bijker, M. Rangachari, S. H. van der Burg, T. Wada, S. Beissert, C. J.M. Melief, and J. M. Penninger (2007)
J. Exp. Med. 204, 879-891
   Abstract »    Full Text »    PDF »
Enhanced Antitumor Activity of T Cells Engineered to Express T-Cell Receptors with a Second Disulfide Bond.
C. J. Cohen, Y. F. Li, M. El-Gamil, P. F. Robbins, S. A. Rosenberg, and R. A. Morgan (2007)
Cancer Res. 67, 3898-3903
   Abstract »    Full Text »    PDF »
c-Met Is a Potentially New Therapeutic Target for Treatment of Human Melanoma.
N. Puri, S. Ahmed, V. Janamanchi, M. Tretiakova, O. Zumba, T. Krausz, R. Jagadeeswaran, and R. Salgia (2007)
Clin. Cancer Res. 13, 2246-2253
   Abstract »    Full Text »    PDF »
Extrathymic Generation of Tumor-Specific T Cells from Genetically Engineered Human Hematopoietic Stem Cells via Notch Signaling.
Y. Zhao, M. R. Parkhurst, Z. Zheng, C. J. Cohen, J. P. Riley, L. Gattinoni, N. P. Restifo, S. A. Rosenberg, and R. A. Morgan (2007)
Cancer Res. 67, 2425-2429
   Abstract »    Full Text »    PDF »
Combining Adoptive Cellular and Immunocytokine Therapies to Improve Treatment of B-Lineage Malignancy.
H. Singh, L. M. Serrano, T. Pfeiffer, S. Olivares, G. McNamara, D. D. Smith, Z. Al-Kadhimi, S. J. Forman, S. D. Gillies, M. C. Jensen, et al. (2007)
Cancer Res. 67, 2872-2880
   Abstract »    Full Text »    PDF »


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