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Submitted on April 20, 2006
Accepted on August 9, 2006
Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes
Richard A. Morgan 1, Mark E. Dudley 1, John R. Wunderlich 1, Marybeth S. Hughes 1, James C. Yang 1, Richard M. Sherry 1, Richard E. Royal 1, Suzanne L. Topalian 1, Udai S. Kammula 1, Nicholas P. Restifo 1, Zhili Zheng 1, Azam Nahvi 1, Christiaan R. de Vries 1, Linda J. Rogers-Freezer 1, Sharon A. Mavroukakis 1, Steven A. Rosenberg 1*
1 Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
* To whom correspondence should be addressed.
Steven A. Rosenberg , E-mail: SAR{at}mail.nih.gov
Using adoptive transfer of lymphocytes given after host immunodepletionit is possible to mediate objective cancer regression in patientswith metastatic melanoma. However, the generation of tumor-specificT cells in this mode of immunotherapy is often limiting. Usinga retrovirus encoding a T cell receptor, we report here theability to specifically confer tumor recognition by autologouslymphocytes from peripheral blood. Adoptive transfer of thesetransduced cells in fifteen patients resulted in durable engraftmentat levels exceeding ten percent of peripheral blood lymphocytesfor at least two months post infusion. We observed high sustainedlevels of circulating, engineered cells at one year post-infusionin two patients, that both demonstrated objective regressionof metastatic melanoma lesions. This study suggests the therapeuticpotential of genetically engineered cells for the biologic therapyof cancer.
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Rienk Offringa (6 October 2006) Science314 (5796), 68.
[DOI: 10.1126/science.1133893] |Summary »|Full Text »|PDF »
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