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Published Online September 19, 2002
Science DOI: 10.1126/science.1076514

Reports

Submitted on July 24, 2002
Accepted on September 6, 2002

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. Rosenberg 1*

1 Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20902, USA.
2 National Eye Institute, National Institutes of Health, Bethesda, MD 20902, USA.
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.

We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor reactive T-cells directed against over-expressed self-derived differentiation antigens following a non-myeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of 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 the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with HIV related AIDS and other infectious diseases.


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Immunotherapy with Chimeric NKG2D Receptors Leads to Long-Term Tumor-Free Survival and Development of Host Antitumor Immunity in Murine Ovarian Cancer.
A. Barber, T. Zhang, and C. L. Sentman (2008)
J. Immunol. 180, 72-78
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Sensitization of Tumor Cells to NK Cell-Mediated Killing by Proteasome Inhibition.
W. H.D. Hallett, E. Ames, M. Motarjemi, I. Barao, A. Shanker, D. L. Tamang, T. J. Sayers, D. Hudig, and W. J. Murphy (2008)
J. Immunol. 180, 163-170
   Abstract »    Full Text »    PDF »
IL-21 mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes.
Y. Li and C. Yee (2008)
Blood 111, 229-235
   Abstract »    Full Text »    PDF »
Induction of hsp70-Mediated Th17 Autoimmunity Can Be Exploited as Immunotherapy for Metastatic Prostate Cancer.
T. Kottke, L. Sanchez-Perez, R. M. Diaz, J. Thompson, H. Chong, K. Harrington, S. K. Calderwood, J. Pulido, N. Georgopoulos, P. Selby, et al. (2007)
Cancer Res. 67, 11970-11979
   Abstract »    Full Text »    PDF »
Sustained Antigen-Specific Antitumor Recall Response Mediated by Gene-Modified CD4+ T Helper-1 and CD8+ T Cells.
M. Moeller, M. H. Kershaw, R. Cameron, J. A. Westwood, J. A. Trapani, M. J. Smyth, and P. K. Darcy (2007)
Cancer Res. 67, 11428-11437
   Abstract »    Full Text »    PDF »
CD8+ Foxp3+ Regulatory T Cells Mediate Immunosuppression in Prostate Cancer.
Y. Kiniwa, Y. Miyahara, H. Y. Wang, W. Peng, G. Peng, T. M. Wheeler, T. C. Thompson, L. J. Old, and R.-F. Wang (2007)
Clin. Cancer Res. 13, 6947-6958
   Abstract »    Full Text »    PDF »
CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15 Dependent Mechanism.
T. Yang, E. M. Wall, K. Milne, P. Theiss, P. Watson, and B. H. Nelson (2007)
Clin. Cancer Res. 13, 7172-7180
   Abstract »    Full Text »    PDF »
Selecting highly affine and well-expressed TCRs for gene therapy of melanoma.
A. Jorritsma, R. Gomez-Eerland, M. Dokter, W. van de Kasteele, Y. M. Zoet, I. I. N. Doxiadis, N. Rufer, P. Romero, R. A. Morgan, T. N. M. Schumacher, et al. (2007)
Blood 110, 3564-3572
   Abstract »    Full Text »    PDF »
How Regulatory CD25+CD4+ T Cells Impinge on Tumor Immunobiology: The Differential Response of Tumors to Therapies.
K. Leon, K. Garcia, J. Carneiro, and A. Lage (2007)
J. Immunol. 179, 5659-5668
   Abstract »    Full Text »    PDF »
Cross-presentation of glycolipid from tumor cells loaded with {alpha}-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells.
K. Shimizu, Y. Kurosawa, M. Taniguchi, R. M. Steinman, and S.-i. Fujii (2007)
J. Exp. Med. 204, 2641-2653
   Abstract »    Full Text »    PDF »
Functional Human Antigen-Specific T Cells Produced In Vitro Using Retroviral T Cell Receptor Transfer into Hematopoietic Progenitors.
A. U. van Lent, M. Nagasawa, M. M. van Loenen, R. Schotte, T. N. M. Schumacher, M. H. M. Heemskerk, H. Spits, and N. Legrand (2007)
J. Immunol. 179, 4959-4968
   Abstract »    Full Text »    PDF »
Warrior, miscreant, suicide: making better killers.
M. E. Dudley (2007)
Blood 110, 2781-2782
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Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes.
C. Quintarelli, J. F. Vera, B. Savoldo, G. M. P. Giordano Attianese, M. Pule, A. E. Foster, H. E. Heslop, C. M. Rooney, M. K. Brenner, and G. Dotti (2007)
Blood 110, 2793-2802
   Abstract »    Full Text »    PDF »
A Comparison and Critical Analysis of Preclinical Anticancer Vaccination Strategies.
J. N. Kochenderfer and R. E. Gress (2007)
Experimental Biology and Medicine 232, 1130-1141
   Abstract »    Full Text »    PDF »
IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells.
S. Liu, G. Lizee, Y. Lou, C. Liu, W. W. Overwijk, G. Wang, and P. Hwu (2007)
Int. Immunol. 19, 1213-1221
   Abstract »    Full Text »    PDF »


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